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

Enhancing host anti-tumor immunity is paramount for advancing cancer immunotherapy. Here, we identify CWF19-like cell cycle control factor 1 (CWF19L1) as a promising immunotherapeutic target that functions as a splicing factor to enhance T cell-mediated cytotoxicity. CWF19L1 interacts prominently with key splicing factors and regulators, including U5 small nuclear ribonucleoprotein (snRNP) and the pre-mRNA processing factor 19 (PRPF19) complex. Deficiency of CWF19L1 leads to aberrant alternative splicing of immune-related genes and repression of cytotoxic molecule expression. Furthermore, CWF19L1 plays a pivotal role in promoting T cell-mediated anti-tumor immunity by upregulating effector cytokine expression. Our findings unveil previously undocumented functions of CWF19L1 in alternative splicing and its crucial involvement in anti-tumor immunity. These insights underscore the potential of targeting CWF19L1 for the development of novel cancer immunotherapies. Overall design: To examine the possible role of CWF19L1 in mRNA splicing, we performed RNA sequencing on control Jurkat cells (shCtrl) and CWF19L1 knockdown Jurkat cells (shCWF19L1).