دورية أكاديمية
Immune heterogeneity in small-cell lung cancer and vulnerability to immune checkpoint blockade.
| العنوان: | Immune heterogeneity in small-cell lung cancer and vulnerability to immune checkpoint blockade. |
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| المؤلفون: | Nabet BY; Genentech Inc., South San Francisco CA, USA. Electronic address: nabet.barzin@gene.com., Hamidi H; Genentech Inc., South San Francisco CA, USA., Lee MC; Genentech Inc., South San Francisco CA, USA., Banchereau R; Genentech Inc., South San Francisco CA, USA., Morris S; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Adler L; F. Hoffmann-La Roche Ltd, Basel, Switzerland., Gayevskiy V; Genentech Inc., South San Francisco CA, USA; Rancho Biosciences, San Diego, CA, USA., Elhossiny AM; Genentech Inc., South San Francisco CA, USA., Srivastava MK; Genentech Inc., South San Francisco CA, USA., Patil NS; Genentech Inc., South San Francisco CA, USA., Smith KA; Genentech Inc., South San Francisco CA, USA., Jesudason R; Genentech Inc., South San Francisco CA, USA., Chan C; Genentech Inc., South San Francisco CA, USA., Chang PS; Genentech Inc., South San Francisco CA, USA., Fernandez M; Genentech Inc., South San Francisco CA, USA., Rost S; Genentech Inc., South San Francisco CA, USA., McGinnis LM; Genentech Inc., South San Francisco CA, USA., Koeppen H; Genentech Inc., South San Francisco CA, USA., Gay CM; Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Minna JD; Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, 6000 Harry Hines Blvd., Dallas, TX 75390-8593, USA; Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX 75390, USA; Departments of Internal Medicine and Pharmacology, UT Southwestern Medical Center, Dallas, TX 75390, USA., Heymach JV; Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Chan JM; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA., Rudin CM; Department of Medicine, Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Program for Computational and Systems Biology, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10016, USA; Weill Cornell Medical College, New York, NY 10065, USA., Byers LA; Department of Thoracic/Head & Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA., Liu SV; Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA., Reck M; Lung Clinic Grosshansdorf, Airway Research Center North, German Center of Lung Research, Grosshansdorf, Germany., Shames DS; Genentech Inc., South San Francisco CA, USA. Electronic address: shames.david@gene.com. |
| المصدر: | Cancer cell [Cancer Cell] 2024 Mar 11; Vol. 42 (3), pp. 429-443.e4. Date of Electronic Publication: 2024 Feb 15. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | Lung Neoplasms*/genetics , Small Cell Lung Carcinoma*/genetics, Humans ; Immune Checkpoint Inhibitors/therapeutic use ; Carboplatin/therapeutic use ; Etoposide/therapeutic use ; Immunotherapy |
| مستخلص: | Atezolizumab (anti-PD-L1), combined with carboplatin and etoposide (CE), is now a standard of care for extensive-stage small-cell lung cancer (ES-SCLC). A clearer understanding of therapeutically relevant SCLC subsets could identify rational combination strategies and improve outcomes. We conduct transcriptomic analyses and non-negative matrix factorization on 271 pre-treatment patient tumor samples from IMpower133 and identify four subsets with general concordance to previously reported SCLC subtypes (SCLC-A, -N, -P, and -I). Deeper investigation into the immune heterogeneity uncovers two subsets with differing neuroendocrine (NE) versus non-neuroendocrine (non-NE) phenotypes, demonstrating immune cell infiltration hallmarks. The NE tumors with low tumor-associated macrophage (TAM) but high T-effector signals demonstrate longer overall survival with PD-L1 blockade and CE versus CE alone than non-NE tumors with high TAM and high T-effector signal. Our study offers a clinically relevant approach to discriminate SCLC patients likely benefitting most from immunotherapies and highlights the complex mechanisms underlying immunotherapy responses. Competing Interests: Declaration of interests B.Y.N., H.H., and D.S.S. are co-inventors on a provisional patent application filed by Genentech/Roche related to this manuscript. B.Y.N. is an employee and stockholder of Roche/Genentech. H.H. is an employee and stockholder of Roche/Genentech. R.B. is an employee and shareholder of Roche/Genentech. S.M. is an employee and shareholder of Roche. L.A. is an employee and shareholder of Roche. V.G. is an employee of Rancho Biosciences and a consultant to Roche/Genentech. M.C.L. is an employee of Roche/Genentech. A.M.E. is an employee of Roche/Genentech. M.K.S. is an employee and shareholder of Roche/Genentech. N.S.P. is an employee and shareholder of Roche/Genentech. K.A.S. is an employee of Roche/Genentech. R.J. is an employee and shareholder of Roche/Genentech. C.C. is an employee and shareholder of Roche/Genentech. P.S.C. is an employee and shareholder of Roche/Genentech. M.F. is an employee of Roche/Genentech. S.R. is an employee and shareholder of Roche/Genentech. L.M.M. is an employee and shareholder of Roche/Genentech. H.K. is an employee and shareholder of Roche/Genentech. J.D.M. receives royalties from the NIH and UTSW for distribution of human tumor cell lines and has the following grants: CA070907, CA213274, and CA213338. C.M.G. reports consulting/advisory fees from AstraZeneca, Bristol Myers Squibb, Catalyst Pharmaceuticals, Daiichi Sankyo, G1 Therapeutics, Insights Driven Research, Jazz Pharmaceuticals, and Monte Rosa Therapeutics, as well as speaking/travel fees from Aptitude Health, BeiGene, DAVA Oncology, MJH, and OncLive, and royalties from UpToDate, Inc. J.M.C. has been paid as a consultant for Sonata Therapeutics and also owns stock in Mirati Therapeutics. J.V.H. has advisory or consulting relationships with Genentech, Mirati Therapeutics, Eli Lilly & Co, Janssen Pharmaceuticals, Boehringer-Ingelheim Pharmaceuticals, Regeneron, Takeda Pharmaceuticals, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca Pharmaceuticals, BioAtla, Sanofi, Spectrum Pharmaceuticals, GlaxoSmithKline, EMD Serono, Blueprint Medicine, and Chugai Pharmaceuticals. C.M.R. has consulted regarding oncology drug development with AbbVie, Amgen, AstraZeneca, D2G, Daiichi Sankyo, Epizyme, Genentech/Roche, Ipsen, Jazz, Kowa, Lilly, Merck, and Syros. He serves on the scientific advisory boards of Auron, Bridge Medicines, DISCO, Earli, and Harpoon Therapeutics. L.A.B. has consulted regarding oncology drug development Merck Sharp & Dohme Corp., Arrowhead Pharmaceuticals, Chugai Pharmaceutical Co., AstraZeneca Pharmaceuticals, Genetech Inc., BeiGene, AbbVie, Jazz Pharmaceuticals, Puma Biotechnology, Amgen, and Daiichi Sankyo. S.V.L. served as a paid consultant/advisor for oncology drug development with AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Blueprint, Boehringer-Ingelheim, Bristol-Myers Squibb, Catalyst, AstraZeneca, D2G, Daiichi Sankyo, Eisai, Elevation Oncology Epizyme, Genentech/Roche, Gilead, Guardant Health, Janssen, Ipsen, Jazz Pharmaceuticals, Kowa, Lilly, Merck/MSD, Novartis, Regeneron, Sanofi, Takeda, Turning Point, and Syros. He serves on the scientific advisory boards of Bridge Medicines, Earli, and Harpoon Therapeutics and has received research funding (to institution). M.R. has received honoraria for lectures and consultancy from Amgen, AstraZeneca, BMS, BeiGene, Boehringer-Ingelheim, Daiichi Sankyo, GSK, Mirati, Merck, MSD, Lilly, Novartis, Pfizer, Regeneron, and Sanofi. He has received compensation for membership of DMSB by Daiichi Sankyo and Sanofi. D.S.S. is an employee and stockholder of Roche/Genentech. (Copyright © 2024 Elsevier Inc. All rights reserved.) |
| فهرسة مساهمة: | Keywords: IMpower133; atezolizumab; immune checkpoint blockade; immunotherapy; molecular subtyping; small cell lung cancer; transcriptomics; tumor-associated macrophages |
| المشرفين على المادة: | 0 (Immune Checkpoint Inhibitors) BG3F62OND5 (Carboplatin) 6PLQ3CP4P3 (Etoposide) |
| تواريخ الأحداث: | Date Created: 20240217 Date Completed: 20240314 Latest Revision: 20240314 |
| رمز التحديث: | 20240314 |
| DOI: | 10.1016/j.ccell.2024.01.010 |
| PMID: | 38366589 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-3686 |
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| DOI: | 10.1016/j.ccell.2024.01.010 |