SPP1 <sup>+</sup> TAM: CD8 <sup>+</sup> T Cell Crosstalk Associates with Blocking Radiotherapy Efficacy in Lung Cancer
Radiotherapy (RT) is a cornerstone treatment for non-small cell lung cancer (NSCLC), but its efficacy is often limited by immune suppression in the tumor microenvironment. In this study, we identified SPP1 as a key factor up-regulated after RT, mainly expressed by immunosuppressive macrophages. Single-cell RNA sequencing and in vivo models showed that SPP1<sup>+</sup> macrophages inhibit CD8<sup>+</sup> T cell infiltration and correlate with poor prognosis. Targeting SPP1 in macrophages enhanced RT efficacy, reduced tumor burden, and restored antitumor immunity. In summary, combining RT with SPP1<sup>+</sup> macrophage-targeted intervention may serve as a promising strategy to overcome immune-mediated radioresistance and enhance therapeutic efficacy in NSCLC.
Authors
- Bufu Tang (ORCID: https://orcid.org/0000-0003-3525-4433)
- Yuzhao Jin
- Yifei Ma
- Songhua Cai (ORCID: https://orcid.org/0000-0003-3839-2030)
- Wenjun Mao (ORCID: https://orcid.org/0000-0002-4644-9749)
- Peng Luo (ORCID: https://orcid.org/0000-0002-8215-2045)
- Zhijun Shen
- Xiaojie Zhang (ORCID: https://orcid.org/0000-0003-1138-7215)
- Yuan Zhuang (ORCID: https://orcid.org/0000-0001-8521-5032)
- Jinhua Luo (ORCID: https://orcid.org/0000-0001-6247-4517)
- Lingling Wang (ORCID: https://orcid.org/0000-0003-0272-2974)
- Qing Li (ORCID: https://orcid.org/0000-0003-3370-471X)
- Dandan Guo (ORCID: https://orcid.org/0009-0008-0578-1551)
- Zhao Xie (ORCID: https://orcid.org/0009-0002-4882-0537)
- Chan Gao
- Rong Gao (ORCID: https://orcid.org/0000-0002-9525-098X)
- N.T. Hang
Institutions
- Shanghai Medical College of Fudan University (CN)
- Dalian Medical University (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Fudan University (CN)
- Wenzhou Medical University (CN)
- National Cancer Center (US)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Zhujiang Hospital (CN)
- Zhongshan Hospital (CN)
- First Affiliated Hospital of Dalian Medical University (CN)
- Wuxi People's Hospital (CN)
- China Medical University (CN)
Publication Details
- Journal
- Research
- Published
- 2025-01-01
- DOI
- https://doi.org/10.34133/research.0851
- Citations
- 1
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 1.05