复旦大学曹志伟小组近日取得一项新成果。他们的研究显示，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。2025年2月20日出版的《癌细胞》发表了这项成果。

该研究团队采用索引（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。

该课题组研究人员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有价值的抵抗，并为潜在的患者分层和个性化治疗提供了见解。

研究人员表示，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。

附：英文原文

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

Author: 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, Hong Hu, Jialei Wang, Yuan Li, Yang Zhang, Zhiwei Cao

Issue&Volume: 2025-02-20

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.

DOI: 10.1016/j.ccell.2025.01.012

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00030-3