ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR300/096/SRR30042996/SRR30042996_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR300/097/SRR30042997/SRR30042997_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR300/098/SRR30042998/SRR30042998_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR300/098/SRR30042998/SRR30042998_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR300/099/SRR30042999/SRR30042999_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR300/096/SRR30042996/SRR30042996_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR300/097/SRR30042997/SRR30042997_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR300/099/SRR30042999/SRR30042999_1.fastq.gzprimaryOK200GenomicsFuDan universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA1142001Homo sapiensxref:PubMed:39542248Enhancing 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).ENAfalseCWF19L1 promotes T-cell cytotoxicity through the regulation of alternative splicingCWF19L1 promotes T-cell cytotoxicity through the regulation of alternative splicing2025-09-242024-08-06PRJNA1142001GSE273485960639542248