{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chava S"],"funding":["HHS | National Institutes of Health (NIH)","NCI NIH HHS","DOD | Department of Defense Education Activity (DoDEA)"],"pagination":["232-274"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12808752"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["18(1)"],"pubmed_abstract":["Natural Killer (NK) cells play a critical role in regulating tumor growth, but our understanding of the mechanisms underlying their anti-tumor activity remains limited. We identified the histone methyltransferase EHMT2 as a key suppressor of NK cell-mediated cytotoxicity. EHMT2 inhibition in cancer cells enhanced NK cell-mediated elimination of diverse cancers, including uveal melanoma, breast cancer, and pancreatic cancer. EHMT2 loss increased AZGP1 and decreased TGF-β1 levels, resulting in the autocrine elevation of NKG2D ligands MICB and ULBP3, chemokines in cancer cells, and the paracrine stimulation of NK cell function. In a syngeneic pancreatic cancer model, EHMT2 inhibition suppressed tumors in an NK cell-dependent manner, as NK cell depletion restored tumor growth. This effect pers"],"journal":["EMBO molecular medicine"],"pubmed_title":["Loss of EHMT2 enhances NK cell-driven anti-tumor immunity through TGF-β1 suppression."],"pmcid":["PMC12808752"],"funding_grant_id":["F31 CA271673","R00CA241110","R01CA271673","R00 CA241110","HT9425-24-1-0593"],"pubmed_authors":["Gupta R","Wajapeyee N","Ma B","Malvi P","DeMarco KD","Bugide S","Ruscetti M","Zajac A","Chava S","Parikh CN","Cai G"],"additional_accession":[]},"is_claimable":false,"name":"Loss of EHMT2 enhances NK cell-driven anti-tumor immunity through TGF-β1 suppression.","description":"Natural Killer (NK) cells play a critical role in regulating tumor growth, but our understanding of the mechanisms underlying their anti-tumor activity remains limited. We identified the histone methyltransferase EHMT2 as a key suppressor of NK cell-mediated cytotoxicity. EHMT2 inhibition in cancer cells enhanced NK cell-mediated elimination of diverse cancers, including uveal melanoma, breast cancer, and pancreatic cancer. EHMT2 loss increased AZGP1 and decreased TGF-β1 levels, resulting in the autocrine elevation of NKG2D ligands MICB and ULBP3, chemokines in cancer cells, and the paracrine stimulation of NK cell function. In a syngeneic pancreatic cancer model, EHMT2 inhibition suppressed tumors in an NK cell-dependent manner, as NK cell depletion restored tumor growth. This effect pers","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-12T04:52:21.325Z","creation":"2026-06-12T03:07:44.676Z"},"accession":"S-EPMC12808752","cross_references":{"pubmed":["41366520"],"doi":["10.1038/s44321-025-00357-6"]}}