Abstract 2100: Integrative spatial analysis reveals tumor heterogeneity and immune colony niche related to clinical-outcomes in small cell lung cancer

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 employed 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 revealed a multi-positive tumor cell neighborhood within ASCL1+ (SCLC-A) subtype, characterized by high SLFN11 expression and associated with poor prognosis. We further developed a cell colony detection algorithm (ColonyMap) and revealed a spatially assembled immune niche consisting of antitumoral macrophages, CD8+ T cells and natural killer T cells (MT2) which highly correlated with superior survival, and predicted 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. Citation Format: Chaoqiang Deng, Changbin Zhu, Tao Hu, Jing Wang, Haiquan Chen. Integrative spatial analysis reveals tumor heterogeneity and immune colony niche related to clinical-outcomes in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2100.