Background: Crosstalk between inflammation and the immune system plays an important role in tumor malignant progression, immune evasion, and immunotherapy efficacy. This study aims to explore the significance of inflammation-associated gene ribosomal-binding protein 1 (RRBP1) in modulating tumor malignant progression and immune escape.
Methods: This study was used transcriptome, proteomic and in vivo anti-programmed death-ligand 1 (PD-L1) antibody CRISPR Cas9 screening data to identify RRBP1 as an inflammation-immune-associated gene in bladder cancer (BC). Immunohistochemistry, single-cell RNA sequencing, multiplex immunofluorescence, flow cytometry, RNA sequencing, and animal experiments were used to study the role of RRBP1 in regulating tumor malignant progression and immunotherapy efficacy.
Results: RRBP1 overexpression promoted the proliferation and metastasis of BC both in vitro and in vivo. RNA sequencing and single-cell RNA sequencing revealed that RRBP1 inhibition activated immune-associated pathways and reshaped the tumor immune microenvironment by altering the infiltration of CD8+ T-cell subpopulations, thereby enhancing antitumor immunity. Mechanistically, RRBP1 inhibition enhances the secretion of CXCL10 by cancer cells, which binds to CXCR3 on CD8+ T cells to promote interferon-γ and Granzyme B expression. Furthermore, genetic and pharmacological inhibition of RRBP1 sensitizes tumors to anti-PD-L1 therapy.
Conclusions: Our findings highlight RRBP1 as an inflammation-immune-associated gene that inhibits tumor progression and improves immunotherapy efficacy by regulating the CXCL10-CXCR3 axis in the tumor microenvironment.
Keywords: Bladder Cancer; Immune Checkpoint Inhibitor.
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