Immune heterogeneity in small-cell lung cancer and vulnerability to immune checkpoint blockade Journal Article
| Authors: | Nabet, B. Y.; Hamidi, H.; Lee, M. C.; Banchereau, R.; Morris, S.; Adler, L.; Gayevskiy, V.; Elhossiny, A. M.; Srivastava, M. K.; Patil, N. S.; Smith, K. A.; Jesudason, R.; Chan, C.; Chang, P. S.; Fernandez, M.; Rost, S.; McGinnis, L. M.; Koeppen, H.; Gay, C. M.; Minna, J. D.; Heymach, J. V.; Chan, J. M.; Rudin, C. M.; Byers, L. A.; Liu, S. V.; Reck, M.; Shames, D. S. |
| Article Title: | Immune heterogeneity in small-cell lung cancer and vulnerability to immune checkpoint blockade |
| Abstract: | 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. © 2024 Elsevier Inc. |
| Keywords: | genetics; carboplatin; etoposide; lung neoplasms; transcriptomics; lung tumor; immunotherapy; small cell lung cancer; small cell lung carcinoma; tumor-associated macrophages; immune checkpoint blockade; immune checkpoint inhibitor; humans; human; immune checkpoint inhibitors; atezolizumab; molecular subtyping; impower133 |
| Journal Title: | Cancer Cell |
| Volume: | 42 |
| Issue: | 3 |
| ISSN: | 1535-6108 |
| Publisher: | Cell Press |
| Date Published: | 2024-03-11 |
| Start Page: | 429 |
| End Page: | 443.e4 |
| Language: | English |
| DOI: | 10.1016/j.ccell.2024.01.010 |
| PUBMED: | 38366589 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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