{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ito Y"],"funding":["Japan Society for the Promotion of Science London","Basic Research Laboratory","Kyoto University Foundation","NCI NIH HHS"],"pagination":["1186-1209"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10164097"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(5)"],"pubmed_abstract":["Tumor heterogeneity is a major barrier to cancer therapy, including immunotherapy. Activated T cells can efficiently kill tumor cells following recognition of MHC class I (MHC-I)-bound peptides, but this selection pressure favors outgrowth of MHC-I-deficient tumor cells. We performed a genome-scale screen to discover alternative pathways for T cell-mediated killing of MHC-I-deficient tumor cells. Autophagy and TNF signaling emerged as top pathways, and inactivation of Rnf31 (TNF signaling) and Atg5 (autophagy) sensitized MHC-I-deficient tumor cells to apoptosis by T cell-derived cytokines. Mechanistic studies demonstrated that inhibition of autophagy amplified proapoptotic effects of cytokines in tumor cells. Antigens from apoptotic MHC-I-deficient tumor cells were efficiently cross-presen"],"journal":["Cancer discovery"],"pubmed_title":["Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell-Secreted Cytokines."],"pmcid":["PMC10164097"],"funding_grant_id":["P01 CA163222","22K20758","P30 CA006516","R01 CA238039","P01 CA236749","R01 CA234018","R01 CA251599"],"pubmed_authors":["Zhang W","Juan TY","Kyrysyuk O","Wucherpfennig KW","Pan D","Ito Y","Zhang X","Doench JG","Pyrdol JW","Liu XS"],"additional_accession":[]},"is_claimable":false,"name":"Addressing Tumor Heterogeneity by Sensitizing Resistant Cancer Cells to T cell-Secreted Cytokines.","description":"Tumor heterogeneity is a major barrier to cancer therapy, including immunotherapy. Activated T cells can efficiently kill tumor cells following recognition of MHC class I (MHC-I)-bound peptides, but this selection pressure favors outgrowth of MHC-I-deficient tumor cells. We performed a genome-scale screen to discover alternative pathways for T cell-mediated killing of MHC-I-deficient tumor cells. Autophagy and TNF signaling emerged as top pathways, and inactivation of Rnf31 (TNF signaling) and Atg5 (autophagy) sensitized MHC-I-deficient tumor cells to apoptosis by T cell-derived cytokines. Mechanistic studies demonstrated that inhibition of autophagy amplified proapoptotic effects of cytokines in tumor cells. Antigens from apoptotic MHC-I-deficient tumor cells were efficiently cross-presen","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 May","modification":"2025-04-04T03:01:11.209Z","creation":"2025-04-04T03:01:11.209Z"},"accession":"S-EPMC10164097","cross_references":{"pubmed":["36811466"],"doi":["10.1158/2159-8290.CD-22-1125","10.1158/2159-8290.cd-22-1125"]}}