A pan-cancer single-cell transcriptomic atlas of human bone metastases

Shuoer Wang; Fen Ma; Dongliang Wang; Qian Yu; Haoyu Zheng; Ziqing Chen; Songjiao Zhao; Lun Xu; Qingrong Ye; Yiwen Tan; Wending Huang; Zhengwang Sun; Zhiqiang Wu; Weiluo Cai; Meng Fang; Mo Cheng; Yingzheng Ji; Yunkui Zhang; Bingxin Gu; Shaoli Song; Yang Chen; Jiwei Zhang; Yang Shao; Wangjun Yan; Yidi Sun

doi:10.1016/j.xcrm.2025.102583

A pan-cancer single-cell transcriptomic atlas of human bone metastases

Cell Rep Med. 2026 Feb 17;7(2):102583. doi: 10.1016/j.xcrm.2025.102583. Epub 2026 Jan 30.

Authors

Shuoer Wang¹, Fen Ma², Dongliang Wang³, Qian Yu⁴, Haoyu Zheng⁵, Ziqing Chen⁶, Songjiao Zhao⁷, Lun Xu⁵, Qingrong Ye⁵, Yiwen Tan⁸, Wending Huang⁵, Zhengwang Sun⁵, Zhiqiang Wu⁵, Weiluo Cai⁵, Meng Fang⁵, Mo Cheng⁵, Yingzheng Ji⁹, Yunkui Zhang¹⁰, Bingxin Gu³, Shaoli Song³, Yang Chen⁶, Jiwei Zhang¹¹, Yang Shao¹², Wangjun Yan¹³, Yidi Sun¹⁴

Affiliations

¹ Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Key Laboratory of Genetic Evolution & Animal Models, Chinese Academy of Sciences, Shanghai 200031, China; Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Key Laboratory of Genetic Evolution & Animal Models, Chinese Academy of Sciences, Shanghai 200031, China; Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
³ Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Shanghai Engineering Research Center of Molecular Imaging Probes, Shanghai 200032, China.
⁴ Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
⁵ Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
⁶ Epigenic Therapeutics, Shanghai 201315, China.
⁷ Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
⁸ Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai 200032, China; National Clinical Research Center for Interventional Medicine& Shanghai Clinical Research Center for Interventional Medicine, Shanghai 200032, China.
⁹ Department of Orthopedic, Naval Medical Center of PLA, Second Military Medical University, Shanghai 200052, China.
¹⁰ Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
¹¹ Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: joezhang@shutcm.edu.cn.
¹² Gynecology Department of Traditional Chinese Medicine, The First Affiliated Hospital of Naval Medical University, Shanghai 200433, China. Electronic address: thierryhenrysy@gmail.com.
¹³ Department of Musculoskeletal Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: yanwj@fudan.edu.cn.
¹⁴ Institute of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Key Laboratory of Genetic Evolution & Animal Models, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: ydsun@ion.ac.cn.

Abstract

Bone is a common site for cancer metastasis, yet the mechanisms driving human spinal bone metastases (BMs) are poorly understood. Here, we obtained a single-cell RNA sequencing (scRNA-seq) atlas of 62 BMs across 13 different origins, along with paired primary tumor and normal bone marrow. Unsupervised clustering of cancer cell functional programs revealed 3 groups with distinct prognosis and tumor microenvironment. Integrative analysis with large-scale primary and metastatic pan-cancer and healthy bone marrow scRNA-seq datasets revealed SELE-positive endothelial cells, osteoblasts, and osteoclasts associated with cancer cell proliferation. We also identified BM-enriched exhausted CD8⁺ T cells with increased expression of immune checkpoint genes. In bone metastatic mouse models, a combined anti-PD-1/TIGIT immune therapy effectively suppressed tumor cell proliferation and significantly enhanced the cytotoxic activity of CD8⁺ T cells. Our results provide a systematic view of the molecular basis of BM and suggest future avenues for immunotherapy optimization for BM patients.

Keywords: bone metastasis; immunotherapy; pan-cancer; single-cell transcriptome atlas.

MeSH terms

Animals
Bone Neoplasms* / genetics
Bone Neoplasms* / immunology
Bone Neoplasms* / pathology
Bone Neoplasms* / secondary
CD8-Positive T-Lymphocytes / immunology
Cell Proliferation
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Single-Cell Analysis* / methods
Transcriptome* / genetics
Tumor Microenvironment / genetics