biostudies-literatureZamarin DU.S. Department of DefenseNational Cancer InstituteMemorial Sloan-Kettering Cancer CenterNCI NIH HHSSwim Across AmericaOvarian Cancer Research FundLudwig Institute for Cancer ResearchDamon Runyon Cancer Research Foundation1413-1428https://www.ebi.ac.uk/biostudies/studies/S-EPMC5873884biostudies-literatureUnknown128(4)Intralesional therapy with oncolytic viruses (OVs) leads to the activation of local and systemic immune pathways, which may present targets for further combinatorial therapies. Here, we used human tumor histocultures as well as syngeneic tumor models treated with Newcastle disease virus (NDV) to identify a range of immune targets upregulated with OV treatment. Despite tumor infiltration of effector T lymphocytes in response to NDV, there was ongoing inhibition through programmed death ligand 1 (PD-L1), acting as a mechanism of early and late adaptive immune resistance to the type I IFN response and T cell infiltration, respectively. Systemic therapeutic targeting of programmed cell death receptor 1 (PD-1) or PD-L1 in combination with intratumoral NDV resulted in the rejection of both treatThe Journal of clinical investigationPD-L1 in tumor microenvironment mediates resistance to oncolytic immunotherapy.PMC5873884GrantProgram grantR01 CA056821OC150111CA056821Cycle for SurvivalP30 CA008748Fellowship awardgrantGigoux MSadekova SZamarin DRicca JMBlumenschein WMWolchok JDOseledchyk AMerghoub TWong JYu YfalsePD-L1 in tumor microenvironment mediates resistance to oncolytic immunotherapy.Intralesional therapy with oncolytic viruses (OVs) leads to the activation of local and systemic immune pathways, which may present targets for further combinatorial therapies. Here, we used human tumor histocultures as well as syngeneic tumor models treated with Newcastle disease virus (NDV) to identify a range of immune targets upregulated with OV treatment. Despite tumor infiltration of effector T lymphocytes in response to NDV, there was ongoing inhibition through programmed death ligand 1 (PD-L1), acting as a mechanism of early and late adaptive immune resistance to the type I IFN response and T cell infiltration, respectively. Systemic therapeutic targeting of programmed cell death receptor 1 (PD-1) or PD-L1 in combination with intratumoral NDV resulted in the rejection of both treat2018-01-01T00:00:00Z2018 Apr2025-04-26T03:40:06.02Z2019-03-26T23:44:11ZS-EPMC58738842950494810.1172/jci9804710.1172/JCI98047