Abstract A131: B7-H1 identifies tumor-reactive effector CD8 T cells susceptible of deletion by agonist PD-L1 antibodies

Abstract

Abstract B7-H1 (aka PD-L1) blocking antibodies have been tested in the treatment of human cancers through blocking B7-H1 expressed by tumor cells; however, its impact on B7-H1 expressed by tumor-reactive CD8+ T cells is still unknown. Here, we report that tumor-reactive CD8+ T cells expressing B7-H1 were functional effector cells. An agonist antibody to PD-L1 deleted B7-H1+ PD-1+ tumor-reactive CD8+ T cells via activation of p38 MAPK, and failed to suppress tumor growth. As activation of p38 MAPK leads to CD8+ T cell apoptosis upon T cell activation, a PD-L1 antibody that activated p38 MAPK enhanced apoptosis of activated CD8+ T cells. An intracellular molecule, DNA-PKcs, was identified in association with B7-H1 and a DNA-PKcs inhibitor increased p38 MAPK activation in wild type but not in B7-H1 deficient CD8+ T cells. Our results suggest B7-H1 suppresses p38 MAPK activation via DNA-PKcs to prevent CD8+ T cell death. To maximize antitumor function, PD-L1 antibodies should be selected to avoid their collateral activation of p38 MAPK in tumor-reactive CD8+ T cells. Citation Format: Siyu Cao, Xin Liu, Xiaosheng Wu, Aaron Mansfield, Haidong Dong. B7-H1 identifies tumor-reactive effector CD8 T cells susceptible of deletion by agonist PD-L1 antibodies [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A131.