Abstract LB-361: Tumor-derived microvesicles promote tumor immune escape through PD-1/PD-L1 interaction

Abstract

Abstract PD-1/PD-L1 pathway blockade is a promising new cancer therapy. Although PD-1/PD-L1 therapy has yielded clinical benefits in several types of cancer, further studies are required to clarify predictive biomarkers for drug efficacy and to understand the fundamental mechanism of PD-1/PD-L1 interaction between host and tumor cells. Here, we show that microvesicles (MVs) derived from lung cancer cells express PD-L1 and play a role in immune escape by reducing T cell activity and promoting tumor growth. The abundance of PD-L1 on MVs represented the quantity of PD-L1 expression on cell surfaces. MVs containing PD-L1 inhibited IFN-γ secretion by Jurkat T cells. The IFN-γ secretion was restored by PD-L1 knockout or masking on the MVs. Both the forced expression of PD-L1 on cells without PD-L1 and treatment with MVs containing PD-L1 enhanced tumor growth in vivo. PD-L1 was present on MVs isolated from the plasma of patients with non-small cell lung cancer, and its abundance in the MVs was correlated with the PD-L1 positivity on tumor tissues. MVs could impair immune functions by reducing cytokine production and inducing apoptosis in CD8+ T cells. Our findings indicate that tumor-derived MVs expressing PD-L1 may be an important mediator of tumor immune escape. Citation Format: Dong Ha Kim, Yun Jung Choi, Seon Ye Kim, Jung-Eun Lee, Ki Jung Sung, Jae Cheol Lee, Jin Kyung Rho. Tumor-derived microvesicles promote tumor immune escape through PD-1/PD-L1 interaction [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-361.