Cancer Cell. 2025 Feb 14:S1535-6108(25)00030-3. doi: 10.1016/j.ccell.2025.01.012. Online ahead of print.

ABSTRACT

Recent advances have shed light on the molecular heterogeneity of small cell lung cancer (SCLC), yet the spatial organizations and cellular interactions in tumor immune microenvironment remain to be elucidated. Here, we employ co-detection by indexing (CODEX) and multi-omics profiling to delineate the spatial landscape for 165 SCLC patients, generating 267 high-dimensional images encompassing over 9.3 million cells. Integrating CODEX and genomic data reveals a multi-positive tumor cell neighborhood within ASCL1⁺ (SCLC-A) subtype, characterized by high SLFN11 expression and associated with poor prognosis. We further develop a cell colony detection algorithm (ColonyMap) and reveal a spatially assembled immune niche consisting of antitumoral macrophages, CD8⁺ T cells and natural killer T cells (MT²) which highly correlates with superior survival and predicts improving immunotherapy response in an independent cohort. This study serves as a valuable resource to study SCLC spatial heterogeneity and offers insights into potential patient stratification and personalized treatments.

PMID:39983726 | DOI:10.1016/j.ccell.2025.01.012