RBM15-mediated metabolic reprogramming boosts immune response in colorectal cancer
文献类型:期刊论文
作者 | Wang, Chen5,6,7; Chen, Mengyan5,6,7; Chen, Panyu4,5,7; Han, Jinlu5,6,7; Hu, Hong5,6,7; Chen, Jiong5,6,7; Wu, Qiong5,7; Zhao, De5,6,7; Wang, Tongshuai6; Zhou, Jingyi3 |
刊名 | FRONTIERS IN IMMUNOLOGY
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出版日期 | 2025-04-30 |
卷号 | 16页码:12 |
关键词 | colorectal cancer RBM15 microenvironment RNA modification m(6)A |
ISSN号 | 1664-3224 |
DOI | 10.3389/fimmu.2025.1515568 |
英文摘要 | Introduction Immune checkpoint blockade (ICB) therapy has shown promise in treating advanced colorectal cancer, particularly in patients with microsatellite instability-high (MSI-H) tumors. However, only a subset of these patients responds favorably, highlighting the need for strategies to improve immunotherapy efficacy. Methods To identify potential regulators of immunotherapy response, we conducted a comprehensive analysis of colorectal cancer datasets from The Cancer Genome Atlas (TCGA). We performed multi-omics analyses and functional assays in both human and murine colorectal cancer cell lines. Additionally, we evaluated tumor growth and immune cell infiltration using syngeneic mouse models. Results Our analysis revealed that RNA binding motif protein 15 (RBM15) is highly expressed in colorectal cancer and correlates with poor patient prognosis. Functional studies demonstrated that RBM15 loss led to increased expression of fumarate hydratase (FH). This led to decreased levels of fumarate, a metabolite known to suppress anti-tumor immune responses. In vivo, RBM15 depletion significantly delayed tumor progression and enhanced CD8(+) T cell infiltration and activation in the tumor microenvironment. Discussion These findings identify RBM15 as a negative regulator of anti-tumor immunity in colorectal cancer. Targeting RBM15 may represent a novel strategy to boost immune responsiveness and improve outcomes for patients undergoing immunotherapy. |
资助项目 | Pujiang Project of Shanghai Magnolia Talent plan[24PJD098] ; National Natural Science Foundation of China[82102802] ; National Natural Science Foundation of China[82170638] ; National Natural Science Foundation of China[82102049] ; Doctoral innovation talent base project[RCJD2021B02] ; Natural Science Foundation of the Science and Technology Commission of Shanghai Municipality[23ZR1458300] ; Key laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology[ZDSYS-2023-02] ; Key laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology[ZDSYS-2023-05] ; Key laboratory for Translational Research and Innovative Therapeutics of Gastrointestinal Oncology[ZDSYS-2021-03] |
WOS研究方向 | Immunology |
语种 | 英语 |
WOS记录号 | WOS:001487719100001 |
出版者 | FRONTIERS MEDIA SA |
源URL | [http://119.78.100.183/handle/2S10ELR8/317920] ![]() |
专题 | 新药研究国家重点实验室 |
通讯作者 | Yang, Jing; Shi, Min; Wang, Yugang |
作者单位 | 1.Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Dept Pathol, Shanghai, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Dept Gen Surg, Shanghai, Peoples R China 3.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Dept Oncol, Sch Med, Shanghai, Peoples R China 4.Chinese Acad Sci, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai, Peoples R China 5.Shanghai Jiao Tong Univ, Tongren Hosp,Sch Med, Key Lab Translat Res & Innovat Therapeut Gastroint, Dept Clin Lab, Shanghai, Peoples R China 6.Shanghai Jiao Tong Univ, Tongren Hosp, Hongqiao Int Inst Med, Sch Med, Shanghai, Peoples R China 7.Shanghai Jiao Tong Univ, Sch Med, Tongren Hosp, Dept Gastroenterol, Shanghai, Peoples R China |
推荐引用方式 GB/T 7714 | Wang, Chen,Chen, Mengyan,Chen, Panyu,et al. RBM15-mediated metabolic reprogramming boosts immune response in colorectal cancer[J]. FRONTIERS IN IMMUNOLOGY,2025,16:12. |
APA | Wang, Chen.,Chen, Mengyan.,Chen, Panyu.,Han, Jinlu.,Hu, Hong.,...&Wang, Yugang.(2025).RBM15-mediated metabolic reprogramming boosts immune response in colorectal cancer.FRONTIERS IN IMMUNOLOGY,16,12. |
MLA | Wang, Chen,et al."RBM15-mediated metabolic reprogramming boosts immune response in colorectal cancer".FRONTIERS IN IMMUNOLOGY 16(2025):12. |
入库方式: OAI收割
来源:上海药物研究所
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