First published October 2, 2018 - More info
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 treated and distant tumors. These findings have implications for the timing of PD-1/PD-L1 blockade in conjunction with OV therapy and highlight the importance of understanding the adaptive mechanisms of immune resistance to specific OVs for the rational design of combinatorial approaches using these agents.
Dmitriy Zamarin, Jacob M. Ricca, Svetlana Sadekova, Anton Oseledchyk, Ying Yu, Wendy M. Blumenschein, Jerelyn Wong, Mathieu Gigoux, Taha Merghoub, Jedd D. Wolchok
Original citation: J Clin Invest. 2018;128(4):1413–1428. https://doi.org/10.1172/JCI98047
Citation for this corrigendum: J Clin Invest. 2018;128(11):5184. https://doi.org/10.1172/JCI125039
Jedd D. Wolchok’s conflict-of-interest information was incomplete. The omitted statement is below.
JDW has acted as a consultant for Adaptive Biotechnologies, Advaxis, Amgen, Apricity, Array BioPharma, Ascentage Pharma, BeiGene, Bristol-Myers Squibb, Celgene, Chugai Pharmaceutical Co., Elucida Oncology Inc., Eli Lilly and Company, F-Star, Genentech, Imvaq Therapeutics Corp., Kleo Pharmaceuticals, MedImmune, Merck, Neon Therapuetics, Ono Pharmaceutical Co., Polaris Pharma, Polynoma, PsiOxus Therapeutics, PureTech Health, Recepta Biopharma SA, Trieza Therapeutics, Sellas Life Sciences, Serametrix Immune Monitoring, Surface Oncology, and Syndax; has received research support from Bristol-Myers Squibb, MedImmune, Merck, Genentech; and has equity in Potenza Therapeutics (cofounder), Tizona Therapeutics (cofounder), Adaptive Biotechnologies, Elucida Oncology Inc., Imvaq Therapeutics Corp., BeiGene, and TriEnza.
The authors regret the error.
See the related article at PD-L1 in tumor microenvironment mediates resistance to oncolytic immunotherapy.