Targeting OxLDL-mediated CD36 + CAF reprogramming potentiates PD-1 immunotherapy in osteosarcoma
CD36⁺ CAFs drive immunosuppressive metabolic reprogramming via the OxLDL-PPARG-ANGPTL4 axis, promoting CD8⁺ T cell exhaustion and resistance to immunotherapy in osteosarcoma. Targeting this pathway with VitE alleviated CAF-mediated immune suppression and enhanced PD-1 blockade responses in preclinical models, providing a rationale for metabolism-based combinatorial strategies in osteosarcoma.
Authors
- Huaiyuan Xu (ORCID: https://orcid.org/0000-0002-2501-4527)
- Hongmin Chen (ORCID: https://orcid.org/0000-0001-7942-5252)
- Anyu Zeng (ORCID: https://orcid.org/0009-0007-8306-6265)
- Weiqing Chen (ORCID: https://orcid.org/0009-0004-9139-2018)
- Jin Wang (ORCID: https://orcid.org/0000-0002-7873-4384)
- Yanyang Xu (ORCID: https://orcid.org/0000-0003-1356-4369)
- Zhihao Chen (ORCID: https://orcid.org/0000-0003-4330-0049)
- Xiaojun Zhu (ORCID: https://orcid.org/0009-0003-4011-3202)
- Chuangzhong Deng (ORCID: https://orcid.org/0000-0001-7697-087X)
- Jinchang Lu
- Qinglian Tang (ORCID: https://orcid.org/0000-0003-0118-0739)
- Anqi Wang (ORCID: https://orcid.org/0000-0002-7182-5427)
- Hao Wu (ORCID: https://orcid.org/0000-0003-1269-7354)
- Guohui Song
- Tianqi Luo (ORCID: https://orcid.org/0000-0002-7756-6374)
- Yihui Song (ORCID: https://orcid.org/0000-0002-1717-9217)
Institutions
- Sun Yat-sen University (CN)
- Guangzhou First People's Hospital (CN)
- Sun Yat-sen University Cancer Center (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Molecular Cancer
- Published
- 2025-12-18
- DOI
- https://doi.org/10.1186/s12943-025-02516-2
- Citations
- 1
- Primary Topic
- Lipid metabolism and disorders
- Type
- article
- Field-Weighted Citation Impact
- 1.39