CWF19L1 promotes T-cell cytotoxicity through the regulation of alternative splicing

Abstract

Effective cancer immunotherapy relies on enhancing the host's immune response, particularly by boosting T cell-mediated cytotoxicity against tumor cells. In this study, we identify CWF19-like cell cycle control factor 1 (CWF19L1) as a novel splicing regulator that enhances T cell-mediated cytotoxicity. CWF19L1 interacts prominently with key splicing factors within the nucleus, including components of the U5 small nuclear ribonucleoprotein and the pre-mRNA processing factor 19 (PRPF19) complex. Deficiency of CWF19L1 disrupts alternative splicing of immune-related genes, resulting in diminished expression of cytotoxic molecules. Furthermore, CWF19L1 plays a critical role in promoting T cell-mediated antitumor responses by upregulating the expression of effector cytokines. Our findings unveil previously undocumented functions of CWF19L1 in alternative splicing and its involvement in the regulation of antitumor immunity, highlighting its potential as a therapeutic target for novel cancer immunotherapies.

Keywords: CWF19L1; alternative splicing; antitumor immunity; cytokine; cytotoxicity; snRNP; spliceosome; splicing; splicing factor; t cell.