{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Joung J"],"funding":["Howard Hughes Medical Institute","NHLBI NIH HHS","NIMH NIH HHS","NHGRI NIH HHS"],"pagination":["1606"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8956604"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(1)"],"pubmed_abstract":["The cellular processes that govern tumor resistance to immunotherapy remain poorly understood. To gain insight into these processes, here we perform a genome-scale CRISPR activation screen for genes that enable human melanoma cells to evade cytotoxic T cell killing. Overexpression of four top candidate genes (CD274 (PD-L1), MCL1, JUNB, and B3GNT2) conferred resistance in diverse cancer cell types and mouse xenografts. By investigating the resistance mechanisms, we find that MCL1 and JUNB modulate the mitochondrial apoptosis pathway. JUNB encodes a transcription factor that downregulates FasL and TRAIL receptors, upregulates the MCL1 relative BCL2A1, and activates the NF-κB pathway. B3GNT2 encodes a poly-N-acetyllactosamine synthase that targets >10 ligands and receptors to disrupt interact"],"journal":["Nature communications"],"pubmed_title":["CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity."],"pmcid":["PMC8956604"],"funding_grant_id":["F31 MH117886","DP1 HL141201","R01 HG009761"],"pubmed_authors":["Zhang F","Cho JH","Deasy R","Tseng YY","Joung J","Nety SP","Larson RC","Singh A","Macrae RK","Maus MV","Kirchgatterer PC"],"additional_accession":[]},"is_claimable":false,"name":"CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity.","description":"The cellular processes that govern tumor resistance to immunotherapy remain poorly understood. To gain insight into these processes, here we perform a genome-scale CRISPR activation screen for genes that enable human melanoma cells to evade cytotoxic T cell killing. Overexpression of four top candidate genes (CD274 (PD-L1), MCL1, JUNB, and B3GNT2) conferred resistance in diverse cancer cell types and mouse xenografts. By investigating the resistance mechanisms, we find that MCL1 and JUNB modulate the mitochondrial apoptosis pathway. JUNB encodes a transcription factor that downregulates FasL and TRAIL receptors, upregulates the MCL1 relative BCL2A1, and activates the NF-κB pathway. B3GNT2 encodes a poly-N-acetyllactosamine synthase that targets >10 ligands and receptors to disrupt interact","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-03-13T10:19:46.805Z","creation":"2025-04-19T17:35:49.932Z"},"accession":"S-EPMC8956604","cross_references":{"pubmed":["35338135"],"doi":["10.1038/s41467-022-29205-8"]}}