GFRAL-Fc disarms GDF15 to reprogram tumor immunity and amplify PD-1 efficacy in hepatocellular carcinoma
Our findings validate GDF15 targeting as a viable strategy to overcome checkpoint inhibitor resistance in HCC. The GFRAL-Fc fusion protein demonstrates multimodal therapeutic benefits through metabolic regulation and immune remodeling, providing a clinically translatable approach to optimize PD-1-based regimens. This study addresses critical gaps in current HCC management and warrants further clinical validation.
Authors
- Minghui Yan (ORCID: https://orcid.org/0000-0002-9628-4938)
- Zhaozhao Li
- Wangqian Zhang (ORCID: https://orcid.org/0000-0002-9596-9417)
- Shuning Wang (ORCID: https://orcid.org/0000-0002-1166-078X)
- Jiaxin Shi (ORCID: https://orcid.org/0000-0003-1065-1918)
- Gege Shi (ORCID: https://orcid.org/0009-0003-1526-9002)
- Yueyuan Qiu
- Kuo Zhang (ORCID: https://orcid.org/0000-0001-9014-5649)
- Yang Xiao (ORCID: https://orcid.org/0000-0001-7588-3424)
- Meng Li (ORCID: https://orcid.org/0000-0002-8000-3003)
- Lei He
- Zhaowei Wang (ORCID: https://orcid.org/0000-0001-6541-144X)
- Fei Xie (ORCID: https://orcid.org/0000-0003-0505-0229)
- Jieyu Zhang (ORCID: https://orcid.org/0000-0003-0492-9514)
- Haichen Du
- Haiyan Cao (ORCID: https://orcid.org/0000-0001-9163-1497)
- Duo Yu
Institutions
- Air Force Medical University (CN)
Publication Details
- Journal
- Cell Communication and Signaling
- Published
- 2025-10-15
- DOI
- https://doi.org/10.1186/s12964-025-02427-1
- Citations
- 3
- Primary Topic
- GDF15 and Related Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 5.00
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Shaanxi Province
- Fourth Military Medical University