2025-08-06 中国科学院(CAS)
<関連情報>
- https://english.cas.cn/newsroom/research_news/life/202508/t20250805_1049184.shtml
- https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00349-0
汎がん免疫療法の抵抗性を克服する候補化合物の優先順位付けのための計算フレームワーク Computational framework for prioritizing candidate compounds overcoming the resistance of pancancer immunotherapy
Fangyoumin Feng ∙ Tian He ∙ Ping Lin ∙ … ∙ Jia Fan ∙ Bo Hu ∙ Hong Li
Cell Reports Medicine Published:August 5, 2025
DOI:https://doi.org/10.1016/j.xcrm.2025.102276
Graphical abstract
Highlights
- Pancancer analysis identifies consistent and predictive immunotherapy-related signatures
- IGeS-BS is developed for prioritizing immunotherapy booster
- IGeS-BS shows excellent performance in computational and experimental validation
- SB-366791 and CGP-60474 boost the efficacy of immunotherapy in liver cancer
Summary
Combination therapy has emerged as an effective approach to overcome resistance to immunotherapy. However, only a small number of drugs have been identified with synergistic effects with immunotherapy. Here, we develop a computational framework (IGeS-BS) to recommend compounds that potentially overcome resistance to immunotherapy. A meta-analysis of approximately 1,000 transcriptomes from immunotherapy patients revealed 33 tumor microenvironment (TME) signatures that can robustly and accurately estimate immunotherapy responses. An immuno-boosting landscape for more than 10,000 compounds and 13 cancer types was subsequently generated on The Cancer Genome Atlas (TCGA) and The Library of Integrated Network-Based Cellular Signatures (LINCS) datasets. Furthermore, the immuno-boosting effects of several high-scoring compounds were evaluated by in vitro and in vivo experiments in hepatocellular carcinoma and other cancer types. The results showed that the two best compounds (SB-366791 and CGP-60474) significantly alleviate the resistance of hepatocellular carcinoma to anti-PD1 therapy by activating immune cells. Collectively, our research provides an efficient framework for discovering compounds that enhance immunotherapy responses.
