高分SCI文摘

2023年

No.5

发布时间：2023-06-14 浏览次数：

字号： + - 14

PubMed

(tuberculosis[Title/Abstract]) OR (lung cancer[Title/Abstract])

Filters applied: from 2023/5/1 - 2023/5/31.

1. Nat Biotechnol. 2023 May 25. doi: 10.1038/s41587-023-01796-7. Online ahead of

print.

An engineered influenza virus to deliver antigens for lung cancer vaccination.

Ji D(#)(1)(2)(3), Zhang Y(#)(4)(5)(6), Sun J(4)(5)(6), Zhang B(4), Ma

W(4)(5)(6), Cheng B(4)(5)(6), Wang X(4)(5)(6), Li Y(4)(5)(6), Mu Y(5), Xu H(5),

Wang Q(4), Zhang C(4)(6), Xiao S(4)(6), Zhang L(4)(6), Zhou D(7)(8)(9).

Author information:

(1)State Key Laboratory of Natural and Biomimetic Drugs, School of

Pharmaceutical Sciences, Peking University, Beijing, China.

jidezhong@bjmu.edu.cn.

(2)Shenzhen Bay Laboratory, Gaoke International Innovation Center, Shenzhen,

China. jidezhong@bjmu.edu.cn.

(3)Peking University Ningbo Institute of Marine Medicines, Ningbo, China.

jidezhong@bjmu.edu.cn.

…

The development of cancer neoantigen vaccines that prime the anti-tumor immune

responses has been hindered in part by challenges in delivery of neoantigens to

the tumor. Here, using the model antigen ovalbumin (OVA) in a melanoma model, we

demonstrate a chimeric antigenic peptide influenza virus (CAP-Flu) system for

delivery of antigenic peptides bound to influenza A virus (IAV) to the lung. We

conjugated attenuated IAVs with the innate immunostimulatory agent CpG and,

after intranasal administration to the mouse lung, observed increased immune

cell infiltration to the tumor. OVA was then covalently displayed on IAV-CPG

using click chemistry. Vaccination with this construct yielded robust antigen

uptake by dendritic cells, a specific immune cell response and a significant

increase in tumor-infiltrating lymphocytes compared to peptides alone. Lastly,

we engineered the IAV to express anti-PD1-L1 nanobodies that further enhanced

regression of lung metastases and prolonged mouse survival after rechallenge.

Engineered IAVs can be equipped with any tumor neoantigen of interest to

generate lung cancer vaccines.

DOI: 10.1038/s41587-023-01796-7

PMID: 37231262

2. Cell. 2023 May 11;186(10):2176-2192.e22. doi: 10.1016/j.cell.2023.04.009. Epub

2023 May 2.

Clp-targeting BacPROTACs impair mycobacterial proteostasis and survival.

Hoi DM(1), Junker S(2), Junk L(3), Schwechel K(4), Fischel K(5), Podlesainski

D(6), Hawkins PME(7), van Geelen L(4), Kaschani F(6), Leodolter J(2), Morreale

FE(2), Kleine S(6), Guha S(8), Rumpel K(5), Schmiedel VM(5), Weinstabl H(5),

Meinhart A(2), Payne RJ(7), Kaiser M(6), Hartl M(9), Boehmelt G(5), Kazmaier

U(10), Kalscheuer R(4), Clausen T(11).

Author information:

(1)Research Institute of Molecular Pathology, Vienna BioCenter, 1030 Vienna,

Austria; Max Perutz Labs, Vienna BioCenter, 1030 Vienna, Austria; Vienna

BioCenter PhD Program, Doctoral School of the University of Vienna and Medical

University of Vienna, 1030 Vienna, Austria; University of Vienna, Center for

Molecular Biology, Department for Biochemistry and Cell Biology, 1030 Vienna,

Austria.

(2)Research Institute of Molecular Pathology, Vienna BioCenter, 1030 Vienna,

Austria.

(3)Saarland University, Organic Chemistry I, 66123 Saarbrücken, Germany;

Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz

Centre for Infection Research (HZI), 66123 Saarbrücken, Germany. Electronic

address: lukas.junk@helmholtz-hips.de.

…

Comment in

Nat Rev Drug Discov. 2023 Jun;22(6):448.

The ClpC1:ClpP1P2 protease is a core component of the proteostasis system in

mycobacteria. To improve the efficacy of antitubercular agents targeting the Clp

protease, we characterized the mechanism of the antibiotics cyclomarin A and

ecumicin. Quantitative proteomics revealed that the antibiotics cause massive

proteome imbalances, including upregulation of two unannotated yet conserved

stress response factors, ClpC2 and ClpC3. These proteins likely protect the Clp

protease from excessive amounts of misfolded proteins or from cyclomarin A,

which we show to mimic damaged proteins. To overcome the Clp security system, we

developed a BacPROTAC that induces degradation of ClpC1 together with its ClpC2

caretaker. The dual Clp degrader, built from linked cyclomarin A heads, was

highly efficient in killing pathogenic Mycobacterium tuberculosis,

with >100-fold increased potency over the parent antibiotic. Together, our data

reveal Clp scavenger proteins as important proteostasis safeguards and highlight

the potential of BacPROTACs as future antibiotics.

DOI: 10.1016/j.cell.2023.04.009

PMID: 37137307 [Indexed for MEDLINE]

3. Nat Genet. 2023 May;55(5):807-819. doi: 10.1038/s41588-023-01355-5. Epub 2023

Apr 6.

Genomic and transcriptomic analysis of checkpoint blockade response in advanced

non-small cell lung cancer.

Ravi A(#)(1)(2), Hellmann MD(#)(3), Arniella MB(#)(1), Holton M(1), Freeman

SS(1), …

Author information:

(1)Broad Institute of Massachusetts Institute of Technology (MIT) and Harvard,

Cambridge, MA, USA.

(2)Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston,

MA, USA.

(3)AstraZeneca, Oncology R&D, New York, NY, USA.

…

Anti-PD-1/PD-L1 agents have transformed the treatment landscape of advanced

non-small cell lung cancer (NSCLC). To expand our understanding of the molecular

features underlying response to checkpoint inhibitors in NSCLC, we describe here

the first joint analysis of the Stand Up To Cancer-Mark Foundation cohort, a

resource of whole exome and/or RNA sequencing from 393 patients with NSCLC

treated with anti-PD-(L)1 therapy, along with matched clinical response

annotation. We identify a number of associations between molecular features and

outcome, including (1) favorable (for example, ATM altered) and unfavorable (for

example, TERT amplified) genomic subgroups, (2) a prominent association between

expression of inducible components of the immunoproteasome and response and (3)

a dedifferentiated tumor-intrinsic subtype with enhanced response to checkpoint

blockade. Taken together, results from this cohort demonstrate the complexity of

biological determinants underlying immunotherapy outcomes and reinforce the

discovery potential of integrative analysis within large, well-curated,

cancer-specific cohorts.

DOI: 10.1038/s41588-023-01355-5

PMCID: PMC10181943

PMID: 37024582 [Indexed for MEDLINE]

4. JAMA. 2023 May 2;329(17):1495-1509. doi: 10.1001/jama.2023.3954.

Screening for Latent Tuberculosis Infection in Adults: Updated Evidence Report

and Systematic Review for the US Preventive Services Task Force.

Jonas DE(1)(2), Riley SR(1)(2), Lee LC(2), Coffey CP(2), Wang SH(2)(3), Asher

GN(1)(4), Berry AM(4)(5), Williams N(4)(6), Balio C(1)(7), Voisin CE(1)(2),

Kahwati LC(1)(8).

Author information:

(1)RTI International-University of North Carolina at Chapel Hill Evidence-based

Practice Center, Research Triangle Park.

(2)Department of Internal Medicine, The Ohio State University College of

Medicine, Columbus.

(3)Global One Health Initiative, The Ohio State University, Columbus.

…

Comment in

JAMA. 2023 May 2;329(17):1457-1459.

JAMA Netw Open. 2023 May 1;6(5):e2312114.

IMPORTANCE: Latent tuberculosis infection (LTBI) can progress to active

tuberculosis disease, causing morbidity and mortality.

OBJECTIVE: To review the evidence on benefits and harms of screening for and

treatment of LTBI in adults to inform the US Preventive Services Task Force

(USPSTF).

DATA SOURCES: PubMed/MEDLINE, Cochrane Library, and trial registries through

December 3, 2021; references; experts; literature surveillance through January

20, 2023.

STUDY SELECTION: English-language studies of LTBI screening, LTBI treatment, or

accuracy of the tuberculin skin test (TST) or interferon-gamma release assays

(IGRAs). Studies of LTBI screening and treatment for public health surveillance

or disease management were excluded.

DATA EXTRACTION AND SYNTHESIS: Dual review of abstracts, full-text articles, and

study quality; qualitative synthesis of findings; meta-analyses conducted when a

sufficient number of similar studies were available.

MAIN OUTCOMES AND MEASURES: Screening test accuracy; development of active

tuberculosis disease, transmission, quality of life, mortality, and harms.

RESULTS: A total of 113 publications were included (112 studies; N = 69 009). No

studies directly evaluated the benefits and harms of screening. Pooled estimates

for sensitivity of the TST were 0.80 (95% CI, 0.74-0.87) at the 5-mm induration

threshold, 0.81 (95% CI, 0.76-0.87) at the 10-mm threshold, and 0.60 (95% CI,

0.46-0.74) at the 15-mm threshold. Pooled estimates for sensitivity of IGRA

tests ranged from 0.81 (95% CI, 0.79-0.84) to 0.90 (95% CI, 0.87-0.92). Pooled

estimates for specificity of screening tests ranged from 0.95 to 0.99. For

treatment of LTBI, a large (n = 27 830), good-quality randomized clinical trial

found a relative risk (RR) for progression to active tuberculosis at 5 years of

0.35 (95% CI, 0.24-0.52) for 24 weeks of isoniazid compared with placebo (number

needed to treat, 112) and an increase in hepatotoxicity (RR, 4.59 [95% CI,

2.03-10.39]; number needed to harm, 279). A previously published meta-analysis

reported that multiple regimens were efficacious compared with placebo or no

treatment. Meta-analysis found greater risk for hepatotoxicity with isoniazid

than with rifampin (pooled RR, 4.22 [95% CI, 2.21-8.06]; n = 7339).

CONCLUSIONS AND RELEVANCE: No studies directly evaluated the benefits and harms

of screening for LTBI compared with no screening. TST and IGRAs were moderately

sensitive and highly specific. Treatment of LTBI with recommended regimens

reduced the risk of progression to active tuberculosis. Isoniazid was associated

with higher rates of hepatotoxicity than placebo or rifampin.

DOI: 10.1001/jama.2023.3954

PMID: 37129650 [Indexed for MEDLINE]

5. JAMA. 2023 May 2;329(17):1487-1494. doi: 10.1001/jama.2023.4899.

Screening for Latent Tuberculosis Infection in Adults: US Preventive Services

Task Force Recommendation Statement.

US Preventive Services Task Force; Mangione CM(1), Barry MJ(2), Nicholson WK(3),

Cabana M(4), Chelmow D(5), Coker TR(6), Davis EM(7), Donahue KE(8), Jaén CR(9),

Li L(10), Ogedegbe G(11), Rao G(12), Ruiz JM(13), Stevermer J(14), Underwood

SM(15), Wong JB(16).

Author information:

(1)University of California, Los Angeles.

(2)Harvard Medical School, Boston, Massachusetts.

(3)George Washington University, Washington, DC.

…

Comment in

JAMA. 2023 May 2;329(17):1457-1459.

JAMA Netw Open. 2023 May 1;6(5):e2312114.

Summary for patients in

JAMA. 2023 May 2;329(17):1526.

IMPORTANCE: In the US, tuberculosis remains an important preventable disease,

including active tuberculosis, which may be infectious, and latent tuberculosis

infection (LTBI), which is asymptomatic and not infectious but can later

progress to active disease. The precise prevalence rate of LTBI in the US is

difficult to determine; however, estimated prevalence is about 5.0%, or up to 13

million persons. Incidence of tuberculosis varies by geography and living

accommodations, suggesting an association with social determinants of health.

OBJECTIVE: To update its 2016 recommendation, the US Preventive Services Task

Force (USPSTF) commissioned a systematic review on LTBI screening and treatment

in asymptomatic adults seen in primary care, as well as the accuracy of LTBI

screening tests.

POPULATION: Asymptomatic adults 18 years or older at increased risk for

tuberculosis.

EVIDENCE ASSESSMENT: The USPSTF concludes with moderate certainty that there is

a moderate net benefit in preventing active tuberculosis disease by screening

for LTBI in persons at increased risk for tuberculosis infection.

RECOMMENDATION: The USPSTF recommends screening for LTBI in populations at

increased risk. (B recommendation).

DOI: 10.1001/jama.2023.4899

PMID: 37129649 [Indexed for MEDLINE]

6. Cancer Cell. 2023 May 24:S1535-6108(23)00171-X. doi:

10.1016/j.ccell.2023.05.006. Online ahead of print.

Senescent alveolar macrophages promote early-stage lung tumorigenesis.

Prieto LI(1), Sturmlechner I(2), Graves SI(3), Zhang C(4), Goplen NP(5), Yi

ES(6), Sun J(7), Li H(4), Baker DJ(8).

Author information:

(1)Department of Biochemistry and Molecular Biology, Mayo Clinic, 200 First St

SW, Rochester, MN 55905, USA; Department of Pediatric and Adolescent Medicine,

Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.

(2)Department of Immunology, Mayo Clinic, 200 First St SW, Rochester, MN 55905,

USA.

(3)Department of Pediatric and Adolescent Medicine, Mayo Clinic, 200 First St

SW, Rochester, MN 55905, USA.

…

Senescent cells play relevant but context-dependent roles during tumorigenesis.

Here, in an oncogenic Kras-driven lung cancer mouse model, we found that

senescent cells, specifically alveolar macrophages, accumulate early in

neoplasia. These macrophages have upregulated expression of p16INK4a and Cxcr1,

are distinct from previously defined subsets and are sensitive to senolytic

interventions, and suppress cytotoxic T cell responses. Their removal attenuates

adenoma development and progression in mice, indicating their

tumorigenesis-promoting role. Importantly, we found that alveolar macrophages

with these properties increase with normal aging in mouse lung and in human lung

adenocarcinoma in situ. Collectively, our study indicates that a subset of

tissue-resident macrophages can support neoplastic transformation through

altering their local microenvironment, suggesting that therapeutic interventions

targeting senescent macrophages may attenuate lung cancer progression during

early stages of disease.

DOI: 10.1016/j.ccell.2023.05.006

PMID: 37267954

7. Lancet Oncol. 2023 May;24(5):e207-e218. doi: 10.1016/S1470-2045(23)00104-3.

Defining the road map to a UK national lung cancer screening programme.

O'Dowd EL(1), Lee RW(2), Akram AR(3), Bartlett EC(4), Bradley SH(5), Brain K(6),

Callister MEJ(7), Chen Y(8), Devaraj A(4), Eccles SR(9), Field JK(10), Fox

J(11), Grundy S(12), Janes SM(13), Ledson M(14), MacKean M(15), Mackie A(16),

McManus KG(17), Murray RL(18), Nair A(19), Quaife SL(20), Rintoul R(21),

Stevenson A(22), Summers Y(23), Wilkinson LS(24), Booton R(25), Baldwin DR(1),

Crosbie P(26).

Author information:

(1)Nottingham University Hospitals NHS Trust, Nottingham, UK.

(2)Early Diagnosis and Detection Centre, National Institute for Health and Care

Research Biomedical Research Centre at the Royal Marsden and Institute of Cancer

Research, London, UK; National Heart and Lung Institute, Imperial College

London, London, UK. Electronic address: richard.lee@rmh.nhs.uk.

(3)Centre for Inflammation Research, Queen's Medical Research Institute,

University of Edinburgh, Edinburgh, UK; Department of Respiratory Medicine,

Royal Infirmary of Edinburgh, Edinburgh, UK.

…

Lung cancer screening with low-dose CT was recommended by the UK National

Screening Committee (UKNSC) in September, 2022, on the basis of data from trials

showing a reduction in lung cancer mortality. These trials provide sufficient

evidence to show clinical efficacy, but further work is needed to prove

deliverability in preparation for a national roll-out of the first major

targeted screening programme. The UK has been world leading in addressing

logistical issues with lung cancer screening through clinical trials,

implementation pilots, and the National Health Service (NHS) England Targeted

Lung Health Check Programme. In this Policy Review, we describe the consensus

reached by a multiprofessional group of experts in lung cancer screening on the

key requirements and priorities for effective implementation of a programme. We

summarise the output from a round-table meeting of clinicians, behavioural

scientists, stakeholder organisations, and representatives from NHS England, the

UKNSC, and the four UK nations. This Policy Review will be an important tool in

the ongoing expansion and evolution of an already successful programme, and

provides a summary of UK expert opinion for consideration by those organising

and delivering lung cancer screenings in other countries.

DOI: 10.1016/S1470-2045(23)00104-3

PMID: 37142382 [Indexed for MEDLINE]

8. Cancer Cell. 2023 May 8;41(5):837-852.e6. doi: 10.1016/j.ccell.2023.03.019. Epub 2023 Apr 21.

Early immune pressure initiated by tissue-resident memory T cells sculpts tumor

evolution in non-small cell lung cancer.

Weeden CE(1), Gayevskiy V(1), Marceaux C(1), Batey D(2), Tan T(3), Yokote K(2),

Ribera NT(4), Clatch A(5), Christo S(5), Teh CE(6), Mitchell AJ(7), Trussart

M(8), Rankin L(6), Obers A(5), McDonald JA(9), Sutherland KD(9), Sharma VJ(10),

Starkey G(11), D'Costa R(12), Antippa P(13), Leong T(14), Steinfort D(15),

Irving L(15), Swanton C(16), Gordon CL(17), Mackay LK(5), Speed TP(18), Gray

DHD(19), Asselin-Labat ML(20).

Author information:

(1)Personalised Oncology Division, Walter and Eliza Hall Institute of Medical

Research, Parkville, VIC, Australia; Department of Medical Biology, the

University of Melbourne, Parkville, VIC, Australia.

(2)Personalised Oncology Division, Walter and Eliza Hall Institute of Medical

Research, Parkville, VIC, Australia.

(3)Immunology Division, Walter and Eliza Hall Institute of Medical Research,

Parkville, VIC, Australia.

…

Tissue-resident memory T (TRM) cells provide immune defense against local

infection and can inhibit cancer progression. However, it is unclear to what

extent chronic inflammation impacts TRM activation and whether TRM cells

existing in tissues before tumor onset influence cancer evolution in humans. We

performed deep profiling of healthy lungs and lung cancers in never-smokers

(NSs) and ever-smokers (ESs), finding evidence of enhanced immunosurveillance by

cells with a TRM-like phenotype in ES lungs. In preclinical models,

tumor-specific or bystander TRM-like cells present prior to tumor onset boosted

immune cell recruitment, causing tumor immune evasion through loss of MHC class

I protein expression and resistance to immune checkpoint inhibitors. In humans,

only tumors arising in ES patients underwent clonal immune evasion, unrelated to

tobacco-associated mutagenic signatures or oncogenic drivers. These data

demonstrate that enhanced TRM-like activity prior to tumor development shapes

the evolution of tumor immunogenicity and can impact immunotherapy outcomes.

DOI: 10.1016/j.ccell.2023.03.019

PMID: 37086716 [Indexed for MEDLINE]

9. Nat Immunol. 2023 May;24(5):855-868. doi: 10.1038/s41590-023-01476-3. Epub 2023 Apr 3.

Antigen-specific B cells direct T follicular-like helper cells into lymphoid

follicles to mediate Mycobacterium tuberculosis control.

Swanson RV(#)(1), Gupta A(#)(1)(2), Foreman TW(3)(4), Lu L(1), Choreno-Parra

JA(5), Mbandi SK(6), Rosa BA(7)(8), Akter S(1)(2), Das S(1), Ahmed M(1)(2),

Garcia-Hernandez ML(9), Singh DK(10), Esaulova E(11), Artyomov MN(11), Gommerman

J(12), Mehra S(3)(10), Zuniga J(5)(13), Mitreva M(7)(8), Scriba TJ(6),

Rangel-Moreno J(9), Kaushal D(14), Khader SA(15)(16).

Author information:

(1)Department of Molecular Microbiology, Washington University in St. Louis, St.

Louis, MO, USA.

(2)Department of Microbiology, University of Chicago, Chicago, IL, USA.

(3)Divisions of Bacteriology and Parasitology, Tulane National Primate Research

Center, Covington, LA, USA.

…

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause

of death. Granuloma-associated lymphoid tissue (GrALT) correlates with

protection during TB, but the mechanisms of protection are not understood.

During TB, the transcription factor IRF4 in T cells but not B cells is required

for the generation of the TH1 and TH17 subsets of helper T cells and follicular

helper T (TFH)-like cellular responses. A population of IRF4+ T cells coexpress

the transcription factor BCL6 during Mtb infection, and deletion of Bcl6

(Bcl6fl/fl) in CD4+ T cells (CD4cre) resulted in reduction of TFH-like cells,

impaired localization within GrALT and increased Mtb burden. In contrast, the

absence of germinal center B cells, MHC class II expression on B cells,

antibody-producing plasma cells or interleukin-10-expressing B cells, did not

increase Mtb susceptibility. Indeed, antigen-specific B cells enhance cytokine

production and strategically localize TFH-like cells within GrALT via

interactions between programmed cell death 1 (PD-1) and its ligand PD-L1 and

mediate Mtb control in both mice and macaques.

DOI: 10.1038/s41590-023-01476-3

PMID: 37012543 [Indexed for MEDLINE]

10. Cell Host Microbe. 2023 May 29:S1931-3128(23)00201-9. doi:

10.1016/j.chom.2023.05.009. Online ahead of print.

Identification of host regulators of Mycobacterium tuberculosis phenotypes

uncovers a role for the MMGT1-GPR156 lipid droplet axis in persistence.

Kalam H(1), Chou CH(1), Kadoki M(2), Graham DB(2), Deguine J(3), Hung DT(4),

Xavier RJ(5).

Author information:

(1)Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for

Computational and Integrative Biology, Massachusetts General Hospital, Harvard

Medical School, Boston, MA 02114, USA.

(2)Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Center for

Computational and Integrative Biology, Massachusetts General Hospital, Harvard

Medical School, Boston, MA 02114, USA; Department of Molecular Biology,

Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

(3)Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

…

The ability of Mycobacterium tuberculosis (Mtb) to establish latency affects

disease and response to treatment. The host factors that influence the

establishment of latency remain elusive. We engineered a multi-fluorescent Mtb

strain that reports survival, active replication, and stressed non-replication

states and determined the host transcriptome of the infected macrophages in

these states. Additionally, we conducted a genome-wide CRISPR screen to identify

host factors that modulated the phenotypic state of Mtb. We validated hits in a

phenotype-specific manner and prioritized membrane magnesium transporter 1

(MMGT1) for a detailed mechanistic investigation. Mtb infection of

MMGT1-deficient macrophages promoted a switch to persistence, upregulated lipid

metabolism genes, and accumulated lipid droplets during infection. Targeting

triacylglycerol synthesis reduced both droplet formation and Mtb persistence.

The orphan G protein-coupled receptor GPR156 is a key inducer of droplet

accumulation in ΔMMGT1 cells. Our work uncovers the role of MMGT1-GPR156-lipid

droplets in the induction of Mtb persistence.

DOI: 10.1016/j.chom.2023.05.009

PMID: 37269834

11. Cell Host Microbe. 2023 May 23:S1931-3128(23)00199-3. doi:

10.1016/j.chom.2023.05.006. Online ahead of print.

Airway T cells are a correlate of i.v. Bacille Calmette-Guerin-mediated

protection against tuberculosis in rhesus macaques.

Darrah PA(1), Zeppa JJ(2), Wang C(3), Irvine EB(4), Bucsan AN(1), Rodgers MA(2),

Pokkali S(1), Hackney JA(1), Kamath M(1), White AG(2), Borish HJ(2), Frye LJ(2),

Tomko J(2), Kracinovsky K(2), Lin PL(5), Klein E(6), Scanga CA(2), Alter G(7),

Fortune SM(4), Lauffenburger DA(8), Flynn JL(2), Seder RA(1), Maiello P(2),

Roederer M(9).

Author information:

(1)Vaccine Research Center, National Institute of Allergy and Infectious

Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

(2)Department of Microbiology and Molecular Genetics, University of Pittsburgh

School of Medicine and Center for Vaccine Research, University of Pittsburgh,

Pittsburgh, PA 15261, USA.

(3)Department of Immunology and Microbiology, University of Colorado, Anschuntz

Medical Campus, Aurora, CO 80045, USA; Department of Biological Engineering,

Massachusetts Institute of Technology, Cambridge, MA 02142, USA.

…

Bacille Calmette-Guerin (BCG), the only approved Mycobacterium tuberculosis

(Mtb) vaccine, provides limited durable protection when administered

intradermally. However, recent work revealed that intravenous (i.v.) BCG

administration yielded greater protection in macaques. Here, we perform a

dose-ranging study of i.v. BCG vaccination in macaques to generate a range of

immune responses and define correlates of protection. Seventeen of 34 macaques

had no detectable infection after Mtb challenge. Multivariate analysis

incorporating longitudinal cellular and humoral immune parameters uncovered an

extensive and highly coordinated immune response from the bronchoalveolar lavage

(BAL). A minimal signature predicting protection contained four BAL immune

features, of which three remained significant after dose correction: frequency

of CD4 T cells producing TNF with interferon γ (IFNγ), frequency of those

producing TNF with IL-17, and the number of NK cells. Blood immune features were

less predictive of protection. We conclude that CD4 T cell immunity and NK cells

in the airway correlate with protection following i.v. BCG.

Published by Elsevier Inc.

DOI: 10.1016/j.chom.2023.05.006

PMID: 37267955

12. Nat Commun. 2023 May 31;14(1):3150. doi: 10.1038/s41467-023-38841-7.

In vivo CRISPR screens reveal Serpinb9 and Adam2 as regulators of immune therapy

response in lung cancer.

Dervovic D(1), Malik AA(1)(2), Chen ELY(1), Narimatsu M(1), Adler N(3),

Afiuni-Zadeh S(1), Krenbek D(4), Martinez S(1), Tsai R(1), Boucher J(5), Berman

JM(1), Teng K(1)(2), Ayyaz A(1)(6), Lü Y(1)(2), Mbamalu G(1), Loganathan

SK(1)(7), Lee J(8), Zhang L(8)(9), Guidos C(10), Wrana J(1)(2), Valipour A(11),

Roux PP(5)(12), Reimand J(2)(3), Jackson HW(1)(2), Schramek D(13)(14).

Author information:

(1)Centre for Molecular and Systems Biology, Lunenfeld-Tanenbaum Research

Institute, Mount Sinai Hospital, Toronto, ON, Canada.

(2)Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

(3)Computational Biology Program, Ontario Institute for Cancer Research,

Toronto, ON, Canada.

…

How the genetic landscape governs a tumor's response to immunotherapy remains

poorly understood. To assess the immune-modulatory capabilities of 573 genes

associated with altered cytotoxicity in human cancers, here we perform

CRISPR/Cas9 screens directly in mouse lung cancer models. We recover the known

immune evasion factors Stat1 and Serpinb9 and identify the cancer testis antigen

Adam2 as an immune modulator, whose expression is induced by KrasG12D and

further elevated by immunotherapy. Using loss- and gain-of-function experiments,

we show that ADAM2 functions as an oncogene by restraining interferon and TNF

cytokine signaling causing reduced presentation of tumor-associated antigens.

ADAM2 also restricts expression of the immune checkpoint inhibitors PDL1, LAG3,

TIGIT and TIM3 in the tumor microenvironment, which might explain why ex vivo

expanded and adoptively transferred cytotoxic T-cells show enhanced cytotoxic

efficacy in ADAM2 overexpressing tumors. Together, direct in vivo CRISPR/Cas9

screens can uncover genetic alterations that control responses to

immunotherapies.

DOI: 10.1038/s41467-023-38841-7

PMCID: PMC10232477

PMID: 37258521 [Indexed for MEDLINE]

13. Nat Commun. 2023 May 26;14(1):3043. doi: 10.1038/s41467-023-38196-z.

Genome-wide association study of lung adenocarcinoma in East Asia and comparison

with a European population.

Shi J(#)(1), Shiraishi K(#)(2), Choi J(#)(3), Matsuo K(#)(4), Chen TY(#)(5), Dai

J(#)(6)(7), Hung RJ(#)(8), Chen K(#)(9), Shu XO(#)(10), Kim YT(11), Landi MT(3),

Lin D(12), Zheng W(10), Yin Z(13), Zhou B(14), Song B(15), Wang J(16)(17), …

Author information:

(1)Division of Cancer Epidemiology and Genetics, National Cancer Institute,

Rockville, MD, USA. jianxin.shi@nih.gov.

(2)Division of Genome Biology, National Cancer Research Institute, Tokyo, Japan.

(3)Division of Cancer Epidemiology and Genetics, National Cancer Institute,

Rockville, MD, USA.

…

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants

explain only a small fraction of lung adenocarcinoma heritability. Here, we

conducted a two-stage genome-wide association study of lung adenocarcinoma of

East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and

identified 12 novel susceptibility variants, bringing the total number to 28 at

25 independent loci. Transcriptome-wide association analyses together with

colocalization studies using a Taiwanese lung expression quantitative trait loci

dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and

ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European

studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same

time, most of our findings in East Asian populations showed no evidence of

association in European populations. In our studies drawn from East Asian

populations, a polygenic risk score based on the 25 loci had a stronger

association in never-smokers vs. individuals with a history of smoking

(Pinteraction = 0.0058). These findings provide new insights into the etiology

of lung adenocarcinoma in individuals from East Asian populations, which could

be important in developing translational applications.

US; foreign copyright protection may apply.

DOI: 10.1038/s41467-023-38196-z

PMCID: PMC10220065

PMID: 37236969 [Indexed for MEDLINE]

14. PLoS Med. 2023 May 22;20(5):e1004237. doi: 10.1371/journal.pmed.1004237.

eCollection 2023 May.

Evaluating systematic targeted universal testing for tuberculosis in primary

care clinics of South Africa: A cluster-randomized trial (The TUTT Trial).

Martinson NA(1)(2), Nonyane BAS(3), Genade LP(1), Berhanu RH(4), Naidoo P(5),

Brey Z(6), Kinghorn A(1), Nyathi S(7), Young K(8), Hausler H(8), Connell L(9),

Lutchminarain K(10)(11), Swe Swe-Han K(10)(11), Vreede H(12), Said M(13)(14),

von Knorring N(15)(16), Moulton LH(2), Lebina L(1)(17); TUTT Trial team.

Author information:

(1)Perinatal HIV Research Unit (PHRU), University of the Witwatersrand,

Johannesburg, South Africa.

(2)Johns Hopkins University Center for TB Research, Baltimore, Maryland, United

States of America.

(3)Johns Hopkins Bloomberg School of Public Health, Department of International

Health, Baltimore, Maryland, United States of America.

…

BACKGROUND: The World Health Organization (WHO) recommends systematic symptom

screening for tuberculosis (TB). However, TB prevalence surveys suggest that

this strategy does not identify millions of TB patients, globally. Undiagnosed

or delayed diagnosis of TB contribute to TB transmission and exacerbate

morbidity and mortality. We conducted a cluster-randomized trial of large urban

and rural primary healthcare clinics in 3 provinces of South Africa to evaluate

whether a novel intervention of targeted universal testing for TB (TUTT) in

high-risk groups diagnosed more patients with TB per month compared to current

standard of care (SoC) symptom-directed TB testing.

METHODS AND FINDINGS: Sixty-two clinics were randomized; with initiation of the

intervention clinics over 6 months from March 2019. The study was prematurely

stopped in March 2020 due to clinics restricting access to patients, and then a

week later due to the Coronavirus Disease 2019 (COVID-19) national lockdown; by

then, we had accrued a similar number of TB diagnoses to that of the power

estimates and permanently stopped the trial. In intervention clinics, attendees

living with HIV, those self-reporting a recent close contact with TB, or a prior

episode of TB were all offered a sputum test for TB, irrespective of whether

they reported symptoms of TB. We analyzed data abstracted from the national

public sector laboratory database using Poisson regression models and compared

the mean number of TB patients diagnosed per clinic per month between the study

arms. Intervention clinics diagnosed 6,777 patients with TB, 20.7 patients with

TB per clinic month (95% CI 16.7, 24.8) versus 6,750, 18.8 patients with TB per

clinic month (95% CI 15.3, 22.2) in control clinics during study months. A

direct comparison, adjusting for province and clinic TB case volume strata, did

not show a significant difference in the number of TB cases between the 2 arms,

incidence rate ratio (IRR) 1.14 (95% CI 0.94, 1.38, p = 0.46). However,

prespecified difference-in-differences analyses showed that while the rate of TB

diagnoses in control clinics decreased over time, intervention clinics had a 17%

relative increase in TB patients diagnosed per month compared to the prior year,

interaction IRR 1.17 (95% CI 1.14, 1.19, p < 0.001). Trial limitations were the

premature stop due to COVID-19 lockdowns and the absence of between-arm

comparisons of initiation and outcomes of TB treatment in those diagnosed with

TB.

CONCLUSIONS: Our trial suggests that the implementation of TUTT in these 3

groups at extreme risk of TB identified more TB patients than SoC and could

assist in reducing undiagnosed TB patients in settings of high TB prevalence.

TRIAL REGISTRATION: South African National Clinical Trials Registry

DOH-27-092021-4901.

under the terms of the Creative Commons Attribution License, which permits

unrestricted use, distribution, and reproduction in any medium, provided the

original author and source are credited.

DOI: 10.1371/journal.pmed.1004237

PMID: 37216385

15. J Clin Invest. 2023 May 18:e167762. doi: 10.1172/JCI167762. Online ahead of

print.

Host genetic background is a barrier to broadly effective vaccine-mediated

protection against tuberculosis.

Lai R(1), Gong DN(2), Williams T(1), Ogunsola AF(1), Cavallo K(3), Lindestam

Arlehamn CS(4), Acolatse S(2), Beamer G(5), Ferris MT(6), Sassetti CM(1),

Lauffenburger DA(2), Behar SM(3).

Author information:

(1)Department of Microbiology and Physiological Systems, University of

Massachusetts Medical School, Wocester, United States of America.

(2)Department of Biological Engineering, Massachusetts Institute of Technology,

Cambridge, United States of America.

(3)Department of Microbiology and Physiological Systems, University of

Massachusetts Medical Center, Worcester, United States of America.

…

Heterogeneity in human immune responses is difficult to model in standard

laboratory mice. To understand how host variation affects BCG-induced immunity

against Mycobacterium tuberculosis, we studied 24 unique Collaborative Cross

(CC) mouse strains, which differ primarily in the genes and alleles they inherit

from founder strains. The CC strains were vaccinated with or without BCG, and

then challenged with aerosolized M. tuberculosis. As BCG protects only half of

the CC strains tested, we conclude that host genetics has a major influence on

BCG-induced immunity against M. tuberculosis infection, making it an important

barrier to vaccine-mediated protection. Importantly, BCG efficacy is dissociable

from inherent susceptibility to TB. T cell immunity was extensively

characterized to identify components associated with protection that were

stimulated by BCG and recalled after Mtb infection. Although considerable

diversity is observed, BCG has little impact on the composition of T cells in

the lung after infection. Instead, variability is largely shaped by host

genetics. BCG-elicited protection against TB correlated with changes in immune

function. Thus, CC mice can be used to define correlates of protection and to

identify vaccine strategies that protect a larger fraction of genetically

diverse individuals instead of optimizing protection for a single genotype. .

DOI: 10.1172/JCI167762

PMID: 37200108

16. J Clin Invest. 2023 May 18:e158630. doi: 10.1172/JCI158630. Online ahead of

print.

Poly(ADP)ribose polymerase 9 mediates early protection against Mycobacterium

tuberculosis infection by regulating type I IFN production.

Thirunavukkarasu S(1), Ahmed M(1), Rosa BA(2), Boothby M(3), Cho SH(3),

Rangel-Moreno J(4), Mbandi SK(5), Schreiber V(6), Gupta A(7), Zúñiga J(8),

Mitreva M(2), Kaushal D(9), Scriba TJ(5), Khader SA(1).

Author information:

(1)Department of Molecular Microbiology, Washington University, St. Louis, St.

Louis, United States of America.

(2)Washington University in St Louis, The McDonnell Genome Institute, St. Louis,

United States of America.

(3)Department of Pathology, Microbiology, and Immunology, Vanderbilt University,

Nashville, United States of America.

…

The ADP ribosyl transferases (PARPs 1-17) regulate diverse cellular processes,

including DNA damage repair. PARPs are classified based on their ability to

catalyze poly-ADP-ribosylation (PARylation) or mono-ADP-ribosylation

(MARylation). While PARP9 mRNA expression is significantly increased in

progressive human tuberculosis (TB), its participation in host immunity to TB is

unknown. Here, we show that PARP9 mRNA encoding the MARylating PARP9 enzyme is

upregulated during TB in humans and mice and provide evidence of a critical

modulatory role for PARP9 in DNA damage, cGAS and type I IFN production during

TB. Thus, Parp9-deficient mice are susceptible to Mtb infection and exhibit

increased TB disease, cGAS expression, cGAMP and type I IFN production along

with upregulation of complement and coagulation pathways. Enhanced Mtb

susceptibility is type I IFN-dependent, as blockade of IFNAR signaling reversed

the enhanced susceptibility of Parp9-/- mice. Thus, in sharp contrast with PARP9

enhancement of type I IFN production in viral infections, this member of the MAR

family plays a protective role by limiting type I IFN responses during TB.

DOI: 10.1172/JCI158630

PMID: 37200107

17. J Clin Oncol. 2023 May 20;41(15):2673-2681. doi: 10.1200/JCO.22.02545.

Prospective Randomized Trial of Docetaxel Versus Best Supportive Care in

Patients With Non-Small-Cell Lung Cancer Previously Treated With Platinum-Based

Chemotherapy.

Shepherd FA(1), Dancey J(1), Ramlau R(1), Mattson K(1), Gralla R(1), O'Rourke

M(1), Levitan N(1), Gressot L(1), Vincent M(1), Burkes R(1), Coughlin S(1), Kim

Y(1), Berille J(1).

Author information:

(1)From the University of TorontoToronto, and London Regional Cancer Centre,

London, Ontario, Canada; Regional Hospital of Lung Disease and Tuberculosis,

Poznan, Poland; Helsinki University, Helsinki, Finland; Alton Ochsner Medical

Foundation, New Orleans, LA; Greenville Memorial Medical Center, Greenville, SC;

University Hospitals of Cleveland, Cleveland, OH; Veterans Affairs Medical

Center, Houston, TX; and Rhône-Poulenc Rorer, Collegeville, PA, and Paris,

France.

Corrected and republished from

J Clin Oncol. 2000 May;18(10):2095-103.

PURPOSE: To evaluate whether treatment with single-agent docetaxel would result

in longer survival than would best supportive care in patients with

non-small-cell lung cancer who had previously been treated with platinum-based

chemotherapy. Secondary end points included assessment of response (docetaxel

arm only), toxicity, and quality of life.

PATIENTS AND METHODS: Patients with performance statuses of 0 to 2 and stage

IIIB/IV non-small-cell lung cancer with either measurable or evaluable lesions

were eligible for entry onto the study if they had undergone one or more

platinum-based chemotherapy regimens and if they had adequate hematology and

biochemistry parameters. They were excluded if they had symptomatic brain

metastases or if they had previously been treated with paclitaxel. Patients were

stratified by performance status and best response to cisplatin chemotherapy and

were then randomized to treatment with docetaxel 100 mg/m2 (49 patients) or 75

mg/m2 (55 patients) or best supportive care. Patients in both arms were assessed

every 3 weeks.

RESULTS: One hundred four patients (103 of whom were eligible for entry onto the

study) were well balanced for prognostic factors. Of 84 patients with measurable

lesions, six (7.1%) achieved partial responses (three patients at each dose

level). Time to progression was longer for docetaxel patients than for best

supportive care patients (10.6 v 6.7 weeks, respectively; P < .001), as was

median survival (7.0 v 4.6 months; log-rank test, P = .047). The difference was

more significant for docetaxel 75 mg/m2 patients, compared with corresponding

best supportive care patients (7.5 v 4.6 months; log-rank test, P = .010; 1-year

survival, 37% v 11%; χ2 test, P = .003). Febrile neutropenia occurred in 11

patients treated with docetaxel 100 mg/m2, three of whom died, and in one

patient treated with docetaxel 75 mg/m2. Grade 3 or 4 nonhematologic toxicity,

with the exception of diarrhea, occurred at a similar rate in both the docetaxel

and best supportive care groups.

CONCLUSION: Treatment with docetaxel is associated with significant prolongation

of survival, and at a dose of 75 mg/m2, the benefits of docetaxel therapy

outweigh the risks.

DOI: 10.1200/JCO.22.02545

PMID: 37196430

18. J Clin Oncol. 2023 May 20;41(15):2682-2690. doi: 10.1200/JCO.22.02546.

Randomized Phase III Trial of Pemetrexed Versus Docetaxel in Patients With

Non-Small-Cell Lung Cancer Previously Treated With Chemotherapy.

Hanna N(1), Shepherd FA(1), Fossella FV(1), Pereira JR(1), De Marinis F(1), von

Pawel J(1), Gatzemeier U(1), Tsao TCY(1), Pless M(1), Muller T(1), Lim HL(1),

Desch C(1), Szondy K(1), Gervais R(1), Shaharyar, Manegold C(1), Paul S(1),

Paoletti P(1), Einhorn L(1), Bunn PA Jr(1).

Author information:

(1)From Indiana University and the Hoosier Oncology Group; Eli Lilly and

Company, Indianapolis, IN; The University of Texas M.D. Anderson Cancer Center,

Houston, TX; University of Colorado Cancer Center, Denver, CO; Virginia Cancer

Institute, Richmond, VA; Princess Margaret Hospital and the University of

Toronto, Toronto, Ontario, Canada; Instituto Arnaldo Vieira de Carvalho, Sao

Paolo, Brazil; San Camillo-Forlanini Hospitals, Rome, Italy; Chang Gung Memorial

Hospital, Taoyuan, Taiwan; University Hospital Basel, Petersgraben Switzerland;

Fachklinik München, Gauting; Hospital Grosshansdorf, Grosshansdorf; Krankenhaus

Hofheim Am Taunus, Hofheim; Thoraxklinik-Heidelberg, Heidelberg, Germany;

National University Hospital, Singapore; Semmelweis Medical University Diosarok,

Budapest, Hungary; Centre Francois Baclesse, Caen, France; Mayo Hospital,

Lahore, Pakistan.

Corrected and republished from

J Clin Oncol. 2004 May 1;22(9):1589-97.

PURPOSE: To compare the efficacy and toxicity of pemetrexed versus docetaxel in

patients with advanced non-small-cell lung cancer (NSCLC) previously treated

with chemotherapy.

PATIENTS AND METHODS: Eligible patients had a performance status 0 to 2,

previous treatment with one prior chemotherapy regimen for advanced NSCLC, and

adequate organ function. Patients received pemetrexed 500 mg/m2 intravenously

(IV) day 1 with vitamin B12, folic acid, and dexamethasone or docetaxel 75 mg/m2

IV day 1 with dexamethasone every 21 days. The primary end point was overall

survival.

RESULTS: Five hundred seventy-one patients were randomly assigned. Overall

response rates were 9.1% and 8.8% (analysis of variance P = .105) for pemetrexed

and docetaxel, respectively. Median progression-free survival was 2.9 months for

each arm, and median survival time was 8.3 versus 7.9 months (P = not

significant) for pemetrexed and docetaxel, respectively. The 1-year survival

rate for each arm was 29.7%. Patients receiving docetaxel were more likely to

have grade 3 or 4 neutropenia (40.2% v 5.3%; P < .001), febrile neutropenia

(12.7% v 1.9%; P < .001), neutropenia with infections (3.3% v 0.0%; P = .004),

hospitalizations for neutropenic fever (13.4% v 1.5%; P < .001),

hospitalizations due to other drug related adverse events (10.5% v 6.4%; P =

.092), use of granulocyte colony-stimulating factor support (19.2% v 2.6%, P <

.001) and all grade alopecia (37.7% v 6.4%; P < .001) compared with patients

receiving pemetrexed.

CONCLUSION: Treatment with pemetrexed resulted in clinically equivalent efficacy

outcomes, but with significantly fewer side effects compared with docetaxel in

the second-line treatment of patients with advanced NSCLC and should be

considered a standard treatment option for second-line NSCLC when available.

DOI: 10.1200/JCO.22.02546

PMID: 37196429

19. Nat Commun. 2023 May 9;14(1):2673. doi: 10.1038/s41467-023-38058-8.

Candida expansion in the gut of lung cancer patients associates with an

ecological signature that supports growth under dysbiotic conditions.

Seelbinder B(#)(1), Lohinai Z(#)(2)(3), Vazquez-Uribe R(4), Brunke S(5), Chen

X(1), Mirhakkak M(1), Lopez-Escalera S(6)(7), Dome B(2)(8)(9), Megyesfalvi

Z(2)(8)(9), Berta J(2), Galffy G(10), Dulka E(10), Wellejus A(6), Weiss GJ(11),

Bauer M(12)(13), Hube B(5)(7), Sommer MOA(4), Panagiotou G(14)(15)(16).

Author information:

(1)Microbiome Dynamics, Leibniz Institute for Natural Product Research and

Infection Biology- Hans Knöll Institute, Jena, Germany.

(2)National Koranyi Institute of Pulmonology, Budapest, Hungary.

(3)Translational Medicine Institute, Semmelweis University, Budapest, Hungary.

…

Candida species overgrowth in the human gut is considered a prerequisite for

invasive candidiasis, but our understanding of gut bacteria promoting or

restricting this overgrowth is still limited. By integrating cross-sectional

mycobiome and shotgun metagenomics data from the stool of 75 male and female

cancer patients at risk but without systemic candidiasis, bacterial communities

in high Candida samples display higher metabolic flexibility yet lower

contributional diversity than those in low Candida samples. We develop machine

learning models that use only bacterial taxa or functional relative abundances

to predict the levels of Candida genus and species in an external validation

cohort with an AUC of 78.6-81.1%. We propose a mechanism for intestinal Candida

overgrowth based on an increase in lactate-producing bacteria, which coincides

with a decrease in bacteria that regulate short chain fatty acid and oxygen

levels. Under these conditions, the ability of Candida to harness lactate as a

nutrient source may enable Candida to outcompete other fungi in the gut.

DOI: 10.1038/s41467-023-38058-8

PMCID: PMC10169812

PMID: 37160893 [Indexed for MEDLINE]

20. ACS Nano. 2023 May 23;17(10):9478-9486. doi: 10.1021/acsnano.3c01664. Epub 2023 May 9.

Amorphous Drug Nanoparticles for Inhalation Therapy of Multidrug-Resistant

Tuberculosis.

Rudolph D(1), Redinger N(2)(3), Schwarz K(4), Li F(5), Hädrich G(5), Cohrs M(6),

Dailey LA(5), Schaible UE(2)(3)(7), Feldmann C(1).

Author information:

(1)Institute of Inorganic Chemistry, Karlsruhe Institute of Technology (KIT),

Engesserstr. 15, 76131 Karlsruhe, Germany.

(2)Research Center Borstel, Leibniz Lung Center, Priority Area Infections,

Division Cellular Microbiology, Parkallee 1-40, 23845 Borstel, Germany.

(3)German Center for Infection Research (DZIF), Site

Hamburg-Lübeck-Borstel-Riems, 23845 Borstel, Germany.

…

Tuberculosis (TB) is one of the most prevalent infectious diseases. The global

TB situation is further complicated by increasing patient numbers infected with

Mycobacterium tuberculosis (M.tb.) strains resistant to either one or two of the

first-line therapeutics, promoted by insufficient treatment length and/or drug

levels due to adverse reactions and reduced patient compliance. An intriguing

approach to improve anti-TB therapy relates to nanocarrier-based drug-delivery

systems, which enhance local drug concentrations at infection sites without

systemic toxicity. Recently developed anti-TB antibiotics, however, are

lipophilic and difficult to transport in aqueous systems. Here, the very

lipophilic TB-antibiotics bedaquiline (BDQ) and BTZ (1,3-benzothiazin-4-one 043)

are prepared as high-dose, amorphous nanoparticles via a solvent-antisolvent

technique. The nanoparticles exhibit mean diameters of 60 ± 13 nm (BDQ) and 62 ± 44

nm (BTZ) and have an extraordinarily high drug load with 69% BDQ and >99% BTZ of

total nanoparticle mass plus a certain amount of surfactant (31% for BDQ,<1% for BTZ)

to make the lipophilic drugs water-dispersible. Suspensions with high drug load (4.1 mg/mL

BDQ, 4.2 mg/mL BTZ) are stable for several weeks. In vitro and in vivo studies employing

M.tb.-infected macrophages and susceptible

C3HeB/FeJ mice show promising activity, which outperforms conventional BDQ/BTZ

solutions (in DMF or DMSO) with an up to 50% higher efficacy upon pulmonary

delivery. In vitro, the BDQ/BTZ nanoparticles demonstrate their ability to cross

the different biological barriers and to reach the site of the intracellular

mycobacteria. In vivo, high amounts of the BDQ/BTZ nanoparticles are found in

the lung and specifically inside granulomas, whereas only low

BDQ/BTZ-nanoparticle levels are observed in spleen or liver. Thus, pulmonary

delivered BDQ/BTZ nanoparticles are promising formulations to improve

antituberculosis treatment.

DOI: 10.1021/acsnano.3c01664

PMCID: PMC10211367

PMID: 37160267 [Indexed for MEDLINE]

21. J Exp Med. 2023 Aug 7;220(8):e20230547. doi: 10.1084/jem.20230547. Epub 2023 May 9.

TB granuloma: CD30 co-stimulation for CD4+ T cell co-operation.

Gress AR(1), Bold TD(1).

Author information:

(1)Department of Medicine, Center for Immunology, University of Minnesota,

Minneapolis, MN, USA.

Comment on

doi: 10.1084/jem.20222090.

Tuberculosis granuloma T cells express an array of mediators including the CD30

co-stimulatory receptor and its ligand, CD153. CD4 T effector cells require

signals through CD30, potentially provided co-operatively by other T cells, to

completely differentiate and protect against disease (Foreman et al., 2023. J.

Exp. Med.https://doi.org/10.1084/jem.20222090).

DOI: 10.1084/jem.20230547

PMCID: PMC10174186

PMID: 37158981 [Indexed for MEDLINE]

22. J Clin Oncol. 2023 May 10;41(14):2458-2466. doi: 10.1200/JCO.22.02544.

Phase III Study Comparing Cisplatin Plus Gemcitabine With Cisplatin Plus

Pemetrexed in Chemotherapy-Naive Patients With Advanced-Stage Non-Small-Cell

Lung Cancer.

Scagliotti GV(1), Parikh P(1), von Pawel J(1), Biesma B(1), Vansteenkiste J(1),

Manegold C(1), Serwatowski P(1), Gatzemeier U(1), Digumarti R(1), Zukin M(1),

Lee JS(1), Mellemgaard A(1), Park K(1), Patil S(1), Rolski J(1), Goksel T(1), de

Marinis F(1), Simms L(1), Sugarman KP(1), Gandara D(1).

Author information:

(1)From the University of Torino, Orbassano; San Camillo-Forlanini Hospitals,

Rome, Italy; Tata Memorial Hospital, Mumbai; Nizam's Institute of Medical

Sciences, Hyderabad; Bangalore Institute of Oncology, Bangalore, India;

Asklepios-Fachkliniken Munchen, Gauting; Heidelberg University Medical Center,

Mannheim; Hospital Grosshansdorf, Grosshansdorf, Germany; Jeroen Bosch

Ziekenhuis, 's-Hertogenbosch, the Netherlands; University Hospital Gasthuisberg,

Leuven, Belgium; Specjalistyczny Szpital Im, Szczecin; Maria Sklodowska-Curie

Memorial Institute, Krakow, Poland; National Cancer Institute-Brazil, Rio de

Janeiro, Brazil; National Cancer Center, Goyang; Samsung Medical Center, Seoul,

South Korea; Herlev University Hospital, Herlev, Denmark; Ege University, Izmir,

Turkey; Eli Lilly & Co, Canada, Toronto, Ontario Canada; Eli Lilly & Co,

Indianapolis, IN; University of California Davis Cancer Center, Sacramento, CA.

Corrected and republished from

J Clin Oncol. 2008 Jul 20;26(21):3543-51.

PURPOSE: Cisplatin plus gemcitabine is a standard regimen for first-line

treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of

pemetrexed plus platinum compounds have also shown activity in this setting.

PATIENTS AND METHODS: This noninferiority, phase III, randomized study compared

the overall survival between treatment arms using a fixed margin method (hazard

ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV

NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1.

Patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1,250 mg/m2 on

days 1 and 8 (n = 863) or cisplatin 75 mg/m2 and pemetrexed 500 mg/m2 on day 1

(n = 862) every 3 weeks for up to six cycles.

RESULTS: Overall survival for cisplatin/pemetrexed was noninferior to

cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR =

0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for

cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with

adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell

carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in

patients with squamous cell histology, there was a significant improvement in

survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v

9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4

neutropenia, anemia, and thrombocytopenia (P ≤ .001); febrile neutropenia (P =

.002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4

nausea (P = .004) was more common.

CONCLUSION: In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy

with better tolerability and more convenient administration than

cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to

show survival differences based on histologic type.

DOI: 10.1200/JCO.22.02544

PMID: 37146426

23. J Natl Cancer Inst. 2023 May 4:djad073. doi: 10.1093/jnci/djad073. Online ahead of print.

Comparison of First-Line Radiosurgery for Small-Cell and Non-Small Cell Lung

Cancer Brain Metastases (Cross-FIRE).

Rusthoven CG(1), Staley AW(2), Gao D(2), Yomo S(3), Bernhardt D(4), Wandrey

N(1), El Shafie R(5)(6), Kraemer A(5)(7)(8), Padilla O(9), Chiang V(10),

…

Author information:

(1)University of Colorado School of Medicine, Dept of Radiation Oncology,

Aurora, Colorado, USA.

(2)University of Colorado Cancer Center, Biostatistics Core, Aurora, Colorado,

USA.

(3)Aizawa Comprehensive Cancer Center, Division of Radiation Oncology, Aizawa

Hospital, Matsumoto, Japan.

…

INTRODUCTION: Historical reservations regarding radiosurgery (SRS) for

small-cell-lung-cancer (SCLC) brain metastases (BrM) include concerns for

short-interval/diffuse CNS-progression, poor prognoses, and increased

neurological mortality specific to SCLC histology. We compared SRS outcomes for

SCLC and non-small-cell-lung-cancer (NSCLC) where SRS is well established.

METHODS: Multicenter first-line SRS outcomes for SCLC and NSCLC from 2000-2022

were retrospectively collected (N=892-SCLC/N=4,785-NSCLC). Data from the

prospective JLGK0901 SRS trial were analyzed as a comparison cohort

(N=98-SCLC/N=794-NSCLC). OS and CNS-progression were analyzed using

Cox-Proportional-Hazard and Fine-Gray models, respectively, with multivariable

(MV) adjustment (including age/sex/performance-status/year/extracranial

disease/BrM-number/BrM-volume). Mutation-stratified analyses were performed in

propensity score-matched (PSM) retrospective cohorts of EGFR/ALK-positive-NSCLC,

mutation-negative-NSCLC, and SCLC.

RESULTS: OS was superior with NSCLC over SCLC in the retrospective dataset

(median-OS, 10.5 vs 8.6 months, MV-p<0.001) and JLGK0901. Hazard estimates for

first CNS-progression favoring NSCLC were similar in both datasets but reached

significance in the retrospective dataset only (MV-HR:0.82 [95%-CI:0.73-0.92],

p=0.001). In the PSM cohorts, there were continued OS advantages for NSCLC

(median-OS, 23.7 [EGFR/ALK-positive-NSCLC] vs 13.6 [mutation-negative-NSCLC] vs

10.4 months [SCLC], pairwise-p-values<0.001), but no significant differences in

CNS-progression. Neurological mortality and number of lesions at CNS-progression

were similar for NSCLC and SCLC patients. Leptomeningeal-progression was

increased in NSCLC patients in the retrospective dataset only (MV-HR:1.61

[95%-CI:1.14-2.26], p=0.007).

CONCLUSION: After SRS, SCLC was associated with shorter OS compared to NSCLC.

CNS progression occurred earlier in SCLC overall but was similar in patients

matched on baseline characteristics. Neurological mortality, lesions at

CNS-progression, and leptomeningeal-progression were comparable. These findings

may better inform clinical decision-making for SCLC patients.

For permissions, please email: journals.permissions@oup.com.

DOI: 10.1093/jnci/djad073

PMID: 37142267

24. J Clin Oncol. 2023 Jun 10;41(17):3249-3259. doi: 10.1200/JCO.22.02509. Epub 2023 May 4.

US Food and Drug Administration Approval Summary: Nivolumab Plus

Platinum-Doublet Chemotherapy for the Neoadjuvant Treatment of Patients With

Resectable Non-Small-Cell Lung Cancer.

Akinboro O(1), Drezner N(1), Amatya A(1), Runyan J(1), Fourie-Zirkelbach J(1),

Zhao M(1), Bi Y(1), Korsah K(1), Mixter B(2), Tang S(1), Larkins E(1), Pazdur

R(1)(2), Beaver JA(1)(2), Singh H(1)(2).

Author information:

(1)Center for Drug Evaluation and Research (CDER), U.S. Food and Drug

Administration, Silver Spring, MD.

(2)Oncology Center of Excellence, U.S. Food and Drug Administration, Silver

Spring, MD.

PURPOSE: On March 4, 2022, the US Food and Drug Administration (FDA) approved

nivolumab plus platinum-doublet chemotherapy for the neoadjuvant treatment of

patients with resectable non-small-cell lung cancer (NSCLC). We discuss the

FDA's review of the key data and regulatory considerations supporting this

approval.

PATIENTS AND METHODS: The approval was based on the results of CheckMate 816, an

international, multiregional, active-controlled trial that randomly assigned 358

patients with resectable NSCLC, stage IB (≥4 cm) to IIIA (N2) per the American

Joint Committee on Cancer seventh staging edition to receive either nivolumab

plus platinum-doublet or platinum-doublet chemotherapy alone for three cycles

before planned surgical resection. The major efficacy end point that supported

this approval was event-free survival (EFS).

RESULTS: At the first planned interim analysis (IA), the hazard ratio (HR) for

EFS was 0.63 (95% CI, 0.45 to 0.87; P = .0052; statistical significance boundary

= .0262) favoring the nivolumab plus chemotherapy arm; the median EFS was 31.6

months (95% CI, 30.2 to not reached) in the nivolumab plus chemotherapy arm

versus 20.8 months (95% CI, 14.0 to 26.7) in the chemotherapy-only arm. At the

time of a prespecified IA for overall survival (OS), 26% of patients had died,

and the HR for OS was 0.57 (95% CI, 0.38 to 0.87; P = .0079; statistical

significance boundary = .0033). Eighty-three percent of patients in the

nivolumab-containing arm versus 75% in the chemotherapy-only arm received

definitive surgery.

CONCLUSION: This approval, the first for any regimen for the neoadjuvant

treatment of NSCLC in the United States, was supported by a statistically

significant and clinically meaningful improvement in EFS with no evidence of

detriment in OS or negative impact on patients' receipt and timing of surgery or

surgical outcomes.

DOI: 10.1200/JCO.22.02509

PMCID: PMC10256356

PMID: 37141544 [Indexed for MEDLINE]

25. PLoS Med. 2023 May 4;20(5):e1004121. doi: 10.1371/journal.pmed.1004121.

eCollection 2023 May.

Hepatitis C care cascade among patients with and without tuberculosis:

Nationwide observational cohort study in the country of Georgia, 2015-2020.

Baliashvili D(1), Blumberg HM(1)(2)(3), Gandhi NR(1)(2)(3), Averhoff F(4),

Benkeser D(5), Shadaker S(6), Gvinjilia L(7), Turdziladze A(8), Tukvadze N(9),

Chincharauli M(9), Butsashvili M(10), Sharvadze L(11)(12), Tsertsvadze T(13),

Zarkua J(14), Kempker RR(3).

Author information:

(1)Department of Epidemiology, Emory University Rollins School of Public Health,

Atlanta, Georgia, United States of America.

(2)Department of Global Health, Emory University Rollins School of Public

Health, Atlanta, Georgia, United States of America.

(3)Division of Infectious Diseases, Department of Medicine, Emory University

School of Medicine, Atlanta, Georgia, United States of America.

…

BACKGROUND: The Eastern European country of Georgia initiated a nationwide

hepatitis C virus (HCV) elimination program in 2015 to address a high burden of

infection. Screening for HCV infection through antibody testing was integrated

into multiple existing programs, including the National Tuberculosis Program

(NTP). We sought to compare the hepatitis C care cascade among patients with and

without tuberculosis (TB) diagnosis in Georgia between 2015 and 2019 and to

identify factors associated with loss to follow-up (LTFU) in hepatitis C care

among patients with TB.

METHODS AND FINDINGS: Using national ID numbers, we merged databases of the HCV

elimination program, NTP, and national death registry from January 1, 2015 to

September 30, 2020. The study population included 11,985 adults (aged ≥18 years)

diagnosed with active TB from January 1, 2015 through December 31, 2019, and

1,849,820 adults tested for HCV antibodies between January 1, 2015 and September

30, 2020, who were not diagnosed with TB during that time. We estimated the

proportion of patients with and without TB who were LTFU at each step of the HCV

care cascade and explored temporal changes. Among 11,985 patients with active

TB, 9,065 (76%) patients without prior hepatitis C treatment were tested for HCV

antibodies, of which 1,665 (18%) had a positive result; LTFU from hepatitis C

care was common, with 316 of 1,557 (20%) patients with a positive antibody test

not undergoing viremia testing and 443 of 1,025 (43%) patients with viremia not

starting treatment for hepatitis C. Overall, among persons with confirmed

viremic HCV infection, due to LTFU at various stages of the care cascade only

28% of patients with TB had a documented cure from HCV infection, compared to

55% among patients without TB. LTFU after positive antibody testing

substantially decreased in the last 3 years, from 32% among patients diagnosed

with TB in 2017 to 12% among those diagnosed in 2019. After a positive HCV

antibody test, patients without TB had viremia testing sooner than patients with

TB (hazards ratio [HR] = 1.46, 95% confidence intervals [CI] [1.39, 1.54], p <

0.001). After a positive viremia test, patients without TB started hepatitis C

treatment sooner than patients with TB (HR = 2.05, 95% CI [1.87, 2.25], p <

0.001). In the risk factor analysis adjusted for age, sex, and case definition

(new versus previously treated), multidrug-resistant (MDR) TB was associated

with an increased risk of LTFU after a positive HCV antibody test (adjusted risk

ratio [aRR] = 1.41, 95% CI [1.12, 1.76], p = 0.003). The main limitation of this

study was that due to the reliance on existing electronic databases, we were

unable to account for the impact of all confounding factors in some of the

analyses.

CONCLUSIONS: LTFU from hepatitis C care after a positive antibody or viremia

test was high and more common among patients with TB than in those without TB.

Better integration of TB and hepatitis C care systems can potentially reduce

LTFU and improve patient outcomes both in Georgia and other countries that are

initiating or scaling up their nationwide hepatitis C control efforts and

striving to provide personalized TB treatment.

freely reproduced, distributed, transmitted, modified, built upon, or otherwise

used by anyone for any lawful purpose. The work is made available under the

Creative Commons CC0 public domain dedication.

DOI: 10.1371/journal.pmed.1004121

PMCID: PMC10194957

PMID: 37141386 [Indexed for MEDLINE]

26. J Clin Oncol. 2023 May 1;41(13):2305-2312. doi: 10.1200/JCO.22.02543.

Randomized Phase II Trial Comparing Bevacizumab Plus Carboplatin and Paclitaxel

With Carboplatin and Paclitaxel Alone in Previously Untreated Locally Advanced

or Metastatic Non-Small-Cell Lung Cancer.

Johnson DH(1), Fehrenbacher L(1), Novotny WF(1), Herbst RS(1), Nemunaitis JJ(1),

Jablons DM(1), Langer CJ(1), DeVore RF 3rd(1), Gaudreault J(1), Damico LA(1),

Holmgren E(1), Kabbinavar F(1).

Author information:

(1)From the Division of Hematology & Oncology, Vanderbilt University Medical

School, Nashville, TN; Department of Thoracic/Head & Neck Medical Oncology, M.D.

Anderson Cancer Center, Houston; US Oncology, Sammons Cancer Center, Baylor

University Medical Center, Mary Crowley Medical Research Center, Dallas, TX;

Kaiser Permanente, Vallejo; Thoracic Oncology Program, University of California

San Francisco/Mount Zion Medical Center; Genentech Inc, South San Francisco, CA;

and Fox Chase Cancer Center, Philadelphia, PA.

Corrected and republished from

J Clin Oncol. 2004 Jun 1;22(11):2184-91.

PURPOSE: To investigate the efficacy and safety of bevacizumab plus carboplatin

and paclitaxel in patients with advanced or recurrent non-small-cell lung

cancer.

PATIENTS AND METHODS: In a phase II trial, 99 patients were randomly assigned to

bevacizumab 7.5 (n = 32) or 15 mg/kg (n = 35) plus carboplatin (area under the

curve = 6) and paclitaxel (200 mg/m2) every 3 weeks or carboplatin and

paclitaxel alone (n = 32). Primary efficacy end points were time to disease

progression and best confirmed response rate. On disease progression, patients

in the control arm had the option to receive single-agent bevacizumab 15 mg/kg

every 3 weeks.

RESULTS: Compared with the control arm, treatment with carboplatin and

paclitaxel plus bevacizumab (15 mg/kg) resulted in a higher response rate (31.5%

v 18.8%), longer median time to progression (7.4 v 4.2 months) and a modest

increase in survival (17.7 v 14.9 months). Of the 19 control patients that

crossed over to single-agent bevacizumab, five experienced stable disease, and

1-year survival was 47%. Bleeding was the most prominent adverse event and was

manifested in two distinct clinical patterns; minor mucocutaneous hemorrhage and

major hemoptysis. Major hemoptysis was associated with squamous cell histology,

tumor necrosis and cavitation, and disease location close to major blood

vessels.

CONCLUSION: Bevacizumab in combination with carboplatin and paclitaxel improved

overall response and time to progression in patients with advanced or recurrent

non-small-cell lung cancer. Patients with nonsquamous cell histology appear to

be a subpopulation with improved outcome and acceptable safety risks.

DOI: 10.1200/JCO.22.02543

PMID: 37126944

27. Mol Cell. 2023 May 4;83(9):1474-1488.e8. doi: 10.1016/j.molcel.2023.04.007. Epub 2023 Apr 27.

Structural and functional basis of the universal transcription factor NusG

pro-pausing activity in Mycobacterium tuberculosis.

Delbeau M(1), Omollo EO(2), Froom R(3), Koh S(1), Mooney RA(2), Lilic M(1),

Brewer JJ(1), Rock J(4), Darst SA(5), Campbell EA(6), Landick R(7).

Author information:

(1)Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY

10065, USA.

(2)Department of Biochemistry, University of Wisconsin-Madison, Madison, WI

53706, USA.

(3)Laboratory of Molecular Biophysics, The Rockefeller University, New York, NY

10065, USA; Laboratory of Host-Pathogen Biology, The Rockefeller University, New

York, NY 10065, USA.

…

Transcriptional pauses mediate regulation of RNA biogenesis. DNA-encoded pause

signals trigger pausing by stabilizing RNA polymerase (RNAP) swiveling and

inhibiting DNA translocation. The N-terminal domain (NGN) of the only universal

transcription factor, NusG/Spt5, modulates pausing through contacts to RNAP and

DNA. Pro-pausing NusGs enhance pauses, whereas anti-pausing NusGs suppress

pauses. Little is known about pausing and NusG in the human pathogen

Mycobacterium tuberculosis (Mtb). We report that MtbNusG is pro-pausing. MtbNusG

captures paused, swiveled RNAP by contacts to the RNAP protrusion and

nontemplate-DNA wedged between the NGN and RNAP gate loop. In contrast,

anti-pausing Escherichia coli (Eco) NGN contacts the MtbRNAP gate loop,

inhibiting swiveling and pausing. Using CRISPR-mediated genetics, we show that

pro-pausing NGN is required for mycobacterial fitness. Our results define an

essential function of mycobacterial NusG and the structural basis of pro- versus

anti-pausing NusG activity, with broad implications for the function of all NusG

orthologs.

DOI: 10.1016/j.molcel.2023.04.007

PMCID: PMC10231689

PMID: 37116494 [Indexed for MEDLINE]

28. ACS Nano. 2023 May 9;17(9):8026-8040. doi: 10.1021/acsnano.2c09323. Epub 2023

Apr 24.

Mapping Immune-Tumor Bidirectional Dialogue Using Ultrasensitive Nanosensors for

Accurate Diagnosis of Lung Cancer.

Ganesh S(1)(2)(3), Dharmalingam P(1)(2)(3), Das S(4), Venkatakrishnan

K(5)(2)(3), Tan B(5)(6)(3).

Author information:

(1)Institute for Biomedical Engineering, Science and Technology (I BEST),

Partnership between Toronto Metropolitan University and St. Michael's Hospital,

Toronto, Ontario M5B 1W8, Canada.

(2)Ultrashort Laser Nanomanufacturing Research Facility, Department of

Mechanical and Industrial Engineering, Toronto Metropolitan University, 350

Victoria Street, Toronto, Ontario M5B 2K3, Canada.

(3)Nano-Bio Interface Facility, Department of Mechanical and Industrial

Engineering, Toronto Metropolitan University, 350 Victoria Street, Toronto,

Ontario M5B 2K3, Canada.

…

Lung cancer is one of the most common cancers with high mortality worldwide

despite the development of molecularly targeted therapies and immunotherapies. A

significant challenge in managing lung cancer is the accurate diagnosis of

cancerous lesions owing to the lack of sensitive and specific biomarkers. The

current procedure necessitates an invasive tissue biopsy for diagnosis and

molecular subtyping, which presents patients with risk, morbidity, anxiety, and

high false-positive rates. The high-risk diagnostic approach has highlighted the

need to search for a reliable, low-risk noninvasive diagnostic approach to

capture lung cancer heterogeneity precisely. The immune interaction profile of

lung cancer is driven by immune cells' distinctive, precise interactions with

the tumor microenvironment. Here, we hypothesize that immune cells, particularly

T cells, can be used for accurate lung cancer diagnosis by exploiting the

distinctive immune-tumor interaction by detecting the immune-diagnostic

signature. We have developed an ultrasensitive T-sense nanosensor to probe these

specific diagnostic signatures using the physical synthesis process of

multiphoton ionization. Our research employed predictive in vitro models of lung

cancers, cancer-associated T cells (PCAT, MCAT) and CSC-associated T cells

(PCSCAT, MCSCAT), from primary and metastatic lung cancer patients to reveal the

immune-diagnostic signature and uncover the molecular, functional, and

phenotypic separation between patient-derived T cells (PDT) and healthy samples.

We demonstrated this by adopting a machine learning model trained with SERS data

obtained using cocultured T cells with preclinical models (CAT, CSCAT) of

primary (H69AR) and metastatic lung cancer (H1915). Interrogating these distinct

signatures with PDT captured the complexity and diversity of the

tumor-associated T cell signature across the patient population, exposing the

clinical feasibility of immune diagnosis in an independent cohort of patient

samples. Thus, our predictive approach using T cells from the patient peripheral

blood showed a highly accurate diagnosis with a specificity and sensitivity of

94.1% and 100%, respectively, for primary lung cancer and 97.9% and 94.4% for

metastatic lung cancer. Our results prove that the immune-diagnostic signature

developed in this study could be used as a clinical technology for cancer

diagnosis and determine the course of clinical management with T cells.

DOI: 10.1021/acsnano.2c09323

PMID: 37093561 [Indexed for MEDLINE]

29. J Clin Oncol. 2023 May 20;41(15):e51-e62. doi: 10.1200/JCO.23.00282. Epub 2023 Apr 6.

Therapy for Stage IV Non-Small-Cell Lung Cancer Without Driver Alterations: ASCO

Living Guideline, Version 2023.1.

Singh N(1), Jaiyesimi IA(2), Ismaila N(3), Leighl NB(4), Mamdani H(5), Phillips

T(6), Owen DH(7).

Author information:

(1)Postgraduate Institute of Medical Education and Research, Chandigarh, India.

(2)Corewell Health William Beaumont University Hospital Royal Oak and Oakland

University William Beaumont School of Medicine, Rochester, MI.

(3)American Society of Clinical Oncology, Alexandria, VA.

…

Update of

J Clin Oncol. 2022 Oct 1;40(28):3323-3343.

Living guidelines are developed for selected topic areas with rapidly evolving

evidence that drives frequent change in recommended clinical practice. Living

guidelines are updated on a regular schedule by a standing expert panel that

systematically reviews the health literature on a continuous basis; as described

in the ASCO Guidelines Methodology Manual. ASCO Living Guidelines follow the

ASCO Conflict of Interest Policy Implementation for Clinical Practice

Guidelines. Living Guidelines and updates are not intended to substitute for

independent professional judgment of the treating provider and do not account

for individual variation among patients. See appendix for disclaimers and other

important information (Appendix 1 and Appendix 2). Updates are published

regularly and can be found at

https://ascopubs.org/nsclc-non-da-living-guideline.

DOI: 10.1200/JCO.23.00282

PMID: 37023387 [Indexed for MEDLINE]

30. J Clin Oncol. 2023 May 20;41(15):e42-e50. doi: 10.1200/JCO.23.00281. Epub 2023 Apr 6.

Therapy for Stage IV Non-Small-Cell Lung Cancer With Driver Alterations: ASCO

Living Guideline, Version 2023.1.

Singh N(1), Jaiyesimi IA(2), Ismaila N(3), Leighl NB(4), Mamdani H(5), Phillips

T(6), Owen DH(7).

Author information:

(1)Postgraduate Institute of Medical Education and Research, Chandigarh, India.

(2)Corewell Health William Beaumont University Hospital Royal Oak and Oakland

University William Beaumont School of Medicine, Rochester, MI.

(3)American Society of Clinical Oncology, Alexandria, VA.

…

Update of

J Clin Oncol. 2022 Oct 1;40(28):3310-3322.