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RBM15-mediated metabolic reprogramming boosts immune response in colorectal cancer
Chen Wang1,2,3, Mengyan Chen1,2,3, Panyu Chen1,3,4
1Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Frontiers in Immunology
|May 15, 2025
Summary
RNA binding motif protein 15 (RBM15) negatively regulates anti-tumor immunity in colorectal cancer. Targeting RBM15 may enhance immunotherapy response in patients with advanced colorectal cancer.
Area of Science:
- Oncology
- Immunology
- Cancer Biology
Background:
- Immune checkpoint blockade (ICB) shows promise for advanced colorectal cancer (CRC), especially in microsatellite instability-high (MSI-H) tumors.
- However, limited patient response necessitates strategies to improve immunotherapy efficacy.
Purpose of the Study:
- To identify novel regulators of immunotherapy response in colorectal cancer.
- To investigate the role of RNA binding motif protein 15 (RBM15) in colorectal cancer progression and anti-tumor immunity.
Main Methods:
- Multi-omics analysis of The Cancer Genome Atlas (TCGA) colorectal cancer datasets.
- Functional assays in human and murine colorectal cancer cell lines.
- Evaluation of tumor growth and immune cell infiltration in syngeneic mouse models.
Main Results:
- RBM15 is highly expressed in colorectal cancer and linked to poor prognosis.
- RBM15 depletion increases fumarate hydratase (FH) expression, reducing fumarate levels and enhancing anti-tumor immunity.
- RBM15 inhibition delays tumor progression and boosts CD8+ T cell infiltration and activation.
Conclusions:
- RBM15 acts as a negative regulator of anti-tumor immunity in colorectal cancer.
- Targeting RBM15 presents a potential therapeutic strategy to improve immunotherapy outcomes for colorectal cancer patients.
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