ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1515568
This article is part of the Research TopicRNA Modifications in Cancer: Unraveling Roles and Therapeutic Potential in Immunity and ImmunotherapyView all 9 articles
RBM15-mediated Metabolic Reprogramming Boosts Immune Response in Colorectal Cancer
Provisionally accepted
Chen Wang1,2
Mengyan Chen1,2Panyu Chen1,3Jinlu Han1,2Jiong Chen1,2Qiong Wu1De Zhao1,2
Tongshuai Wang2Jing Yang1*Min Shi1*Yugang Wang1*- 1Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 2Hongqiao International Institute of Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
- 3Shanghai Institute of Materia Medica, Chinese Academy of Sciences (CAS), Shanghai, Shanghai Municipality, China
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Immune checkpoint blockade (ICB) offers therapeutic opportunities for patients with advanced colorectal cancer; however, only a subset of patients with microsatellite instability-high (MSI-H) tumors respond to treatment. Therefore, strategies to enhance immunotherapy sensitivity are urgently needed. In this study, we analyzed the Cancer Genome Atlas (TCGA) datasets and demonstrated that RNA binding motif protein 15 (RBM15) was highly expressed in colorectal cancer and was associated with poor prognosis. Through multi-omics analysis combined with functional experiments, we showed that loss of RBM15 increased the expression of fumarate hydratase (FH) in human and murine colorectal cancer cells, leading to a reduction in its metabolic substrate fumarate, which acts as a suppressor of anti-tumor immunity. Notably, by applying syngeneic mouse models, we found that RBM15 depletion delayed tumor growth by promoting CD8+ T cell infiltration and activation. Our findings identify RBM15 as a key suppressor of anti-tumor immunity, suggesting that targeting RBM15 could be a promising therapeutic strategy in colorectal cancer.
Keywords: colorectal cancer, RBM15, Tumor micro environment, RNA modification, M6A
Received: 23 Oct 2024; Accepted: 07 Apr 2025.
Copyright: © 2025 Wang, Chen, Chen, Han, Chen, Wu, Zhao, Wang, Yang, Shi and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jing Yang, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Min Shi, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Yugang Wang, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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