{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wei SC"],"funding":["NIH Cancer Center","NIDDK NIH HHS","NHLBI NIH HHS","Cancer Prevention and Research in Texas","NCI NIH HHS","the Vanderbilt Mouse Metabolic Phenotyping Center","NIH","NCI Cancer Center","NIH HHS","NIGMS NIH HHS"],"pagination":["614-625"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8041233"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(3)"],"pubmed_abstract":["Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss of <i>Ctla4</i> in the context of complete genetic absence of <i>Pdcd1</i> leads to premature death in approximately half of mice. Premature death results from myocardial infiltration by T cells and macrophages and severe ECG abnormalities, closely recapitulating the clinical and pathologic hallmarks of ICI-associated myocarditis observed in patients. Using this model, we show that <i>Ctla4</i> and <i>Pdcd1</i> functionally interact in a gene dosage-dependent manner, providing a mechanism by which myocarditis arise"],"journal":["Cancer discovery"],"pubmed_title":["A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitor-Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention."],"pmcid":["PMC8041233"],"funding_grant_id":["5P30 CA68485–19","T32 GM152284","F30CA236157","R01 HL155990","U24 DK059637","P30CA16672","R35 HL144980","F30 CA236157","T32 GM007347","R1203","T32 GM007569","2 U24 DK059637–16","P30 CA016672","S10 OD023475","R01 HL141466","R01 CA227481","P30 CA068485","R01CA227481","U2C DK059637","R56 141466","T32GM007347","R56 HL141466","R01 141466"],"pubmed_authors":["Anang NAS","Meijers WC","Rao X","Wescott EC","Courand PY","Wang J","Zhao Y","Axelrod ML","Knollmann BC","Himmel LE","Lehmann L","Whitley E","Atolagbe OT","Moslehi JJ","Balko JM","Ehrlich LIR","Wei SC","Srinivasan J","Allison JP","Sharma P","Mancuso JJ","Johnson DB","Lebrun-Vignes B","Li Y","Screever EM","Wleklinski MJ","Salem JE"],"additional_accession":[]},"is_claimable":false,"name":"A Genetic Mouse Model Recapitulates Immune Checkpoint Inhibitor-Associated Myocarditis and Supports a Mechanism-Based Therapeutic Intervention.","description":"Immune checkpoint inhibitors (ICI) targeting CTLA4 or PD-1/PD-L1 have transformed cancer therapy but are associated with immune-related adverse events, including myocarditis. Here, we report a robust preclinical mouse model of ICI-associated myocarditis in which monoallelic loss of <i>Ctla4</i> in the context of complete genetic absence of <i>Pdcd1</i> leads to premature death in approximately half of mice. Premature death results from myocardial infiltration by T cells and macrophages and severe ECG abnormalities, closely recapitulating the clinical and pathologic hallmarks of ICI-associated myocarditis observed in patients. Using this model, we show that <i>Ctla4</i> and <i>Pdcd1</i> functionally interact in a gene dosage-dependent manner, providing a mechanism by which myocarditis arise","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2026-05-02T11:36:49.091Z","creation":"2022-02-11T10:06:14.126Z"},"accession":"S-EPMC8041233","cross_references":{"pubmed":["33257470"],"doi":["10.1158/2159-8290.CD-20-0856","10.1158/2159-8290.cd-20-0856"]}}