{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Shi H"],"funding":["University of Texas Southwestern Medical Center","NIAID NIH HHS","NCI NIH HHS","National Institutes of Health","NIH HHS"],"pagination":["e20240797"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11528124"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["221(12)"],"pubmed_abstract":["Immune checkpoint inhibitors interfere with T cell exhaustion but often fail to cure or control cancer long-term in patients. Using a genetic screen in C57BL/6J mice, we discovered a mutation in host H2-Aa that caused strong immune-mediated resistance to mouse melanomas. H2-Aa encodes an MHC class II α chain, and its absence in C57BL/6J mice eliminates all MHC-II expression. H2-Aa deficiency, specifically in dendritic cells (DC), led to a quantitative increase in type 2 conventional DC (cDC2) and a decrease in cDC1. H2-Aa-deficient cDC2, but not cDC1, were essential for melanoma suppression and effectively cross-primed and recruited CD8 T cells into tumors. Lack of T regulatory cells, also observed in H2-Aa deficiency, contributed to melanoma suppression. Acute disruption of H2-Aa was therapeutic in melanoma-bearing mice, particularly when combined with checkpoint inhibition, which had no therapeutic effect by itself. Our findings suggest that inhibiting MHC-II may be an effective immunotherapeutic approach to enhance immune responses to cancer."],"journal":["The Journal of experimental medicine"],"pubmed_title":["Suppression of melanoma by mice lacking MHC-II: Mechanisms and implications for cancer immunotherapy."],"pmcid":["PMC11528124"],"funding_grant_id":["R01 AI125581","AI125581","CA258602","R01 CA258602"],"pubmed_authors":["Duran Bojorquez C","Moresco EMY","Schneider S","Medler D","Xing C","Quan J","Wang J","Li X","Beutler B","Moresco JJ","Ludwig S","Liu A","Kumar A","Shi H","Browning R"],"additional_accession":[]},"is_claimable":false,"name":"Suppression of melanoma by mice lacking MHC-II: Mechanisms and implications for cancer immunotherapy.","description":"Immune checkpoint inhibitors interfere with T cell exhaustion but often fail to cure or control cancer long-term in patients. Using a genetic screen in C57BL/6J mice, we discovered a mutation in host H2-Aa that caused strong immune-mediated resistance to mouse melanomas. H2-Aa encodes an MHC class II α chain, and its absence in C57BL/6J mice eliminates all MHC-II expression. H2-Aa deficiency, specifically in dendritic cells (DC), led to a quantitative increase in type 2 conventional DC (cDC2) and a decrease in cDC1. H2-Aa-deficient cDC2, but not cDC1, were essential for melanoma suppression and effectively cross-primed and recruited CD8 T cells into tumors. Lack of T regulatory cells, also observed in H2-Aa deficiency, contributed to melanoma suppression. Acute disruption of H2-Aa was therapeutic in melanoma-bearing mice, particularly when combined with checkpoint inhibition, which had no therapeutic effect by itself. Our findings suggest that inhibiting MHC-II may be an effective immunotherapeutic approach to enhance immune responses to cancer.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-07-09T10:53:18.831Z","creation":"2025-04-06T09:32:07.263Z"},"accession":"S-EPMC11528124","cross_references":{"pubmed":["39470607"],"doi":["10.1084/jem.20240797"]}}