{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nielsen AJ"],"funding":["BLRD VA","NCI NIH HHS"],"pagination":["e180278"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11645140"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["134(24)"],"pubmed_abstract":["Effective antitumor T cell activity relies on the expression and MHC presentation of tumor neoantigens. Tumor cells can evade T cell detection by silencing the transcription of antigens or by altering MHC machinery, resulting in inadequate neoantigen-specific T cell activation. We identified the DNA-protein kinase inhibitor (DNA-PKi) NU7441 as a promising immunomodulator that reduced immunosuppressive proteins, while increasing MHC-I expression in a panel of human melanoma cell lines. In tumor-bearing mice, combination therapy using NU7441 and the immune adjuvants stimulator of IFN genes (STING) ligand and the CD40 agonist NU-SL40 substantially increased and diversified the neoantigen landscape, antigen-presenting machinery, and, consequently, substantially increased both the number and re"],"journal":["The Journal of clinical investigation"],"pubmed_title":["DNA-PK inhibition enhances neoantigen diversity and increases T cell responses to immunoresistant tumors."],"pmcid":["PMC11645140"],"funding_grant_id":["P30 CA046934","R01 CA271537","R01 CA207913","I01 BX004935"],"pubmed_authors":["Couts K","Albert GK","Liu J","McCarter M","Chen J","Nielsen AJ","Davila E","Wilky BA","Robinson W","Geng D","Amato C","Hintzsche JD","Sanchez A","Tobin R","Davalos AS","Bradeen X"],"additional_accession":[]},"is_claimable":false,"name":"DNA-PK inhibition enhances neoantigen diversity and increases T cell responses to immunoresistant tumors.","description":"Effective antitumor T cell activity relies on the expression and MHC presentation of tumor neoantigens. Tumor cells can evade T cell detection by silencing the transcription of antigens or by altering MHC machinery, resulting in inadequate neoantigen-specific T cell activation. We identified the DNA-protein kinase inhibitor (DNA-PKi) NU7441 as a promising immunomodulator that reduced immunosuppressive proteins, while increasing MHC-I expression in a panel of human melanoma cell lines. In tumor-bearing mice, combination therapy using NU7441 and the immune adjuvants stimulator of IFN genes (STING) ligand and the CD40 agonist NU-SL40 substantially increased and diversified the neoantigen landscape, antigen-presenting machinery, and, consequently, substantially increased both the number and re","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2025-04-04T02:33:14.161Z","creation":"2025-04-04T02:33:14.161Z"},"accession":"S-EPMC11645140","cross_references":{"pubmed":["39436696"],"doi":["10.1172/JCI180278"]}}