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

Haiquan Chen¹, Chaoqiang Deng², Jian Gao³, Jun Wang⁴, Fangqiu Fu³, Yue Wang⁵, Qiming Wang⁴, Mou Zhang⁴, Shiyue Zhang⁴, Fanfan Fan³, Kun Liu³, Bo Yang⁶, Qiming He⁶, Qiang Zheng⁵, Xuxia Shen⁵, Jin Wang⁷, Tao Hu⁷, Changbin Zhu⁷, Fei Yang⁸, Yonghong He⁶, Hong Hu³, Jialei Wang⁹, Yuan Li¹⁰, Yang Zhang¹¹, Zhiwei Cao¹²

Affiliations

¹ Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: hqchen1@yahoo.com.
² Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: fdudengcq@163.com.
³ Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
⁴ School of Life Sciences, Fudan University, Shanghai 200032, China.
⁵ Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
⁶ Department of Life and Health, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
⁷ Department of Translational Medicine, Amoy Diagnostics Co., Ltd, Xiamen 361000, China.
⁸ Janssen China Research & Development, Shanghai 200233, China.
⁹ Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address: luwangjialei@126.com.
¹⁰ Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address: lumoxuan2009@163.com.
¹¹ Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: fduzhangyang1987@hotmail.com.
¹² School of Life Sciences, Fudan University, Shanghai 200032, China. Electronic address: zwcao@fudan.edu.cn.

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

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

Haiquan Chen et al. Cancer Cell. 2025.

. 2025 Mar 10;43(3):519-536.e5.

doi: 10.1016/j.ccell.2025.01.012. Epub 2025 Feb 20.

Authors

Affiliations

¹ Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: hqchen1@yahoo.com.
² Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: fdudengcq@163.com.
³ Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
⁴ School of Life Sciences, Fudan University, Shanghai 200032, China.
⁵ Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
⁶ Department of Life and Health, Shenzhen International Graduate School, Tsinghua University, Shenzhen 518055, China.
⁷ Department of Translational Medicine, Amoy Diagnostics Co., Ltd, Xiamen 361000, China.
⁸ Janssen China Research & Development, Shanghai 200233, China.
⁹ Department of Thoracic Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address: luwangjialei@126.com.
¹⁰ Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai 200032, China. Electronic address: lumoxuan2009@163.com.
¹¹ Department of Thoracic Surgery and State Key Laboratory of Genetic Engineering, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Thoracic Oncology, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: fduzhangyang1987@hotmail.com.
¹² School of Life Sciences, Fudan University, Shanghai 200032, China. Electronic address: zwcao@fudan.edu.cn.

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

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.

Keywords: CODEX; cell colony; immunotherapy response; molecular heterogeneity; prognostic marker; spatial atlas; tumor microenvironment.

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Conflict of interest statement

Declaration of interests J.W., T.H., and C.Z. are employees of Amoy Diagnostics Co., Ltd. F.Y. is employee of Janssen China R&D.

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Research Materials