Integrated multi-omics analysis reveals a glycolytic signature that predicts pan-cancer immune checkpoint inhibitor response and LDHA as a combinatorial target in fumarate hydratase-deficient renal cell carcinoma
This study establishes Glyc.Sig as a dual diagnostic-predictive biomarker system, linking glycolytic reprogramming to immune evasion. Comparative validation revealed its enhanced predictive capacity for ICI responsiveness relative to existing molecular signatures. LDHA inhibition emerges as a promising strategy to overcome ICI resistance in FH-deficient RCC and other glycolytic tumors. These findings underscore the therapeutic potential of targeting cancer metabolism to optimize immunotherapy efficacy.
Authors
- Junzhe He
- Yuan Wang (ORCID: https://orcid.org/0000-0002-5692-2659)
- Jianfeng Wang (ORCID: https://orcid.org/0000-0002-0414-6774)
- Jing Zhang (ORCID: https://orcid.org/0000-0002-9231-0844)
- Yunlong Yuan
- Songyang Liu (ORCID: https://orcid.org/0000-0002-4202-5850)
- Yihan Zhou (ORCID: https://orcid.org/0009-0007-6042-6045)
- Xinqi Ye
Institutions
- China Pharmaceutical University (CN)
- Shanghai Jiao Tong University (CN)
- Anhui University of Science and Technology (CN)
- Renji Hospital (CN)
Publication Details
- Journal
- Frontiers in Immunology
- Published
- 2025-10-03
- DOI
- https://doi.org/10.3389/fimmu.2025.1666121
- Citations
- 1
- Primary Topic
- Renal cell carcinoma treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.52
Funders
- National Natural Science Foundation of China
- Shanghai Jiao Tong University
- Renji Hospital
- School of Medicine, Shanghai Jiao Tong University