S100A9 promotes resistance to anti-PD-1 immunotherapy in hepatocellular carcinoma by degrading PARP1 and activating the STAT3/PD-L1 pathway
Our study reveals that S100A9 facilitates immune evasion in HCC by enhancing PARP1 ubiquitination, STAT3 phosphorylation, and PD-L1 expression. Furthermore, combining S100A9 inhibitors with anti-PD-1 antibodies markedly enhances the therapeutic efficacy of ICIs in HCC. These findings highlight S100A9 as a potential therapeutic target for overcoming resistance to immunotherapy in HCC.
Authors
- Zengling Lian (ORCID: https://orcid.org/0000-0003-1087-6981)
- Xitai Sun
- Xuehui Chu
- Yanjun Lu (ORCID: https://orcid.org/0009-0004-0582-0929)
- Binghua Li (ORCID: https://orcid.org/0000-0001-7209-2854)
- Decai Yu (ORCID: https://orcid.org/0000-0002-3006-2531)
- Xiaodong Shan
- Yunzheng Li (ORCID: https://orcid.org/0000-0002-4541-1909)
- Zhu Xu (ORCID: https://orcid.org/0009-0007-9345-7753)
- Yajing Yang (ORCID: https://orcid.org/0009-0006-6950-142X)
- Jingxin Liu (ORCID: https://orcid.org/0000-0001-6637-6076)
- Huan Li (ORCID: https://orcid.org/0000-0003-0736-9292)
- Weihong Wang (ORCID: https://orcid.org/0000-0002-7389-635X)
- Qiao Chu (ORCID: https://orcid.org/0000-0001-7491-310X)
- Xianwei Zhou
- Hon‐Wah Man
Institutions
- Jiangsu University (CN)
- Nanjing University of Chinese Medicine (CN)
- Anhui Medical University (CN)
- Nanjing Drum Tower Hospital (CN)
- Model Animal Research Center (CN)
- First Affiliated Hospital of Anhui Medical University (CN)
Publication Details
- Journal
- Cellular Oncology
- Published
- 2025-07-14
- DOI
- https://doi.org/10.1007/s13402-025-01087-0
- Citations
- 3
- Primary Topic
- S100 Proteins and Annexins
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- Nanjing Drum Tower Hospital