A pan-cancer single-cell transcriptomic atlas of human bone metastases
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<sup>+</sup> 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<sup>+</sup> T cells. Our results provide a systematic view of the molecular basis of BM and suggest future avenues for immunotherapy optimization for BM patients.
Authors
- Meng Fang (ORCID: https://orcid.org/0009-0000-0122-416X)
- Fen Ma (ORCID: https://orcid.org/0000-0002-5680-6121)
- Zhiqiang Wu
- Yifan Tan (ORCID: https://orcid.org/0000-0002-7322-297X)
- Qingrong Ye
- Shuoer Wang (ORCID: https://orcid.org/0000-0003-4315-1776)
- Yingzheng Ji
- Yidi Sun (ORCID: https://orcid.org/0000-0002-2157-1983)
- Weiluo Cai
- Songjiao Zhao (ORCID: https://orcid.org/0000-0001-5666-0508)
- Bingxin Gu (ORCID: https://orcid.org/0000-0001-8813-836X)
- Haoyu Zheng (ORCID: https://orcid.org/0000-0001-7997-3646)
- Lun Xu
- Wending Huang
- Mo Cheng (ORCID: https://orcid.org/0009-0005-8529-1875)
- Jiwei Zhang
- Ziqing Chen
- Qian Yu
- Yang Chen
- Yang Shao
- Yunkui Zhang
- Dongliang Wang
- Zhengwang Sun
- Wangjun Yan
- Shaoli Song
Institutions
- Second Military Medical University (CN)
- Shanghai Jiao Tong University (CN)
- Dalian Medical University (CN)
- Fudan University Shanghai Cancer Center (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Center for Excellence in Brain Science and Intelligence Technology (CN)
- Shanghai University of Traditional Chinese Medicine (CN)
- First Affiliated Hospital of Hunan University of Traditional Chinese Medicine (CN)
- Shanghai First People's Hospital (CN)
- Shanghai Clinical Research Center (CN)
- Chongqing Medical University (CN)
- Epigenomics (Germany) (DE)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2026-01-30
- DOI
- https://doi.org/10.1016/j.xcrm.2025.102583
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00