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. 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).