Immune heterogeneity in small-cell lung cancer and vulnerability to immune checkpoint blockade.
Cancer Cell
; 42(3): 429-443.e4, 2024 Mar 11.
Article
in En
| MEDLINE
| ID: mdl-38366589
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Small Cell Lung Carcinoma
/
Lung Neoplasms
Limits:
Humans
Language:
En
Journal:
Cancer Cell
/
Cancer cell
Journal subject:
NEOPLASIAS
Year:
2024
Type:
Article