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

IF 44.5 1区医学 Q1 CELL BIOLOGY Cancer Cell Pub Date : 2025-02-20 DOI:10.1016/j.ccell.2025.01.012

Haiquan Chen, Chaoqiang Deng, Jian Gao, Jun Wang, Fangqiu Fu, Yue Wang, Qiming Wang, Mou Zhang, Shiyue Zhang, Fanfan Fan, Kun Liu, Bo Yang, Qiming He, Qiang Zheng, Xuxia Shen, Jin Wang, Tao Hu, Changbin Zhu, Fei Yang, Yonghong He, Zhiwei Cao

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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.

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综合空间分析揭示小细胞肺癌的肿瘤异质性和免疫菌落生态位与临床结果相关

近年来，小细胞肺癌（small cell lung cancer， SCLC）的分子异质性得到了揭示，但肿瘤免疫微环境中的空间组织和细胞相互作用仍有待阐明。在这里，我们采用索引（CODEX）和多组学分析的共同检测来描绘165名SCLC患者的空间景观，生成267张高维图像，包含超过930万个细胞。综合CODEX和基因组数据，发现ASCL1+ (SCLC-A)亚型中存在多阳性肿瘤细胞邻域，其特点是SLFN11高表达，预后差。我们进一步开发了一种细胞集落检测算法（ColonyMap），并揭示了一个由抗肿瘤巨噬细胞、CD8+ T细胞和自然杀伤T细胞（MT2）组成的空间组装免疫生态位，它与更高的生存率高度相关，并在一个独立的队列中预测改善的免疫治疗反应。该研究为研究SCLC的空间异质性提供了宝贵的资源，并为潜在的患者分层和个性化治疗提供了见解。

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.