Ribonuclease 1 Induces T-Cell Dysfunction and Impairs CD8⁺ T-Cell Cytotoxicity to Benefit Tumor Growth through Hijacking STAT1.

ABSTRACT: T-cell-based immunotherapy holds promise for eliminating cancer through T-cell activation. However, prolonged interaction between T cells and tumors and the presence of immunosuppressive factors can diminish T-cell cytotoxicity, leading to treatment failure. Here, ribonuclease 1 (RNase1), which degrades RNA, reduced the expression of effector cytokines and increases immune checkpoint protein levels, inducing T-cell dysfunction. RNase1 expression is positively associated with exhausted T-cell gene signatures and immune checkpoint proteins across several cancer types. Cancer cells expressing RNase1 are resistant to CD8⁺ T-cell-mediated killing. RNase1 promotes tumor growth in immunocompetent, but not in immunodeficient, mouse models and inhibits CD8⁺ T-cell activity in

SUBMITTER: Yang WH 

PROVIDER: S-EPMC11967817 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature