Abstract 5241: p38 MAPK/EGR1/PD-L1 axis promotes radiation resistance of nasopharyngeal carcinoma by enhancing immune evasion

Abstract

Abstract Radiation resistance is the main reason for treatment failure. Till present, the underlying molecular mechanism of NPC radiation resistance remains poorly understood. Recent clinical trials have demonstrated that PD-1/PD-L1 inhibitors have achieved better efficacy in the treatment of recurrent or metastatic NPC. Further studies are needed to better understand the molecular mechanisms underlying PD-1/PD-L1 inhibitors enhance response to radiation in NPC. We performed RNA-seq analysis in NPC radioresistant and wild-type cells. We identified EGR1 promotes NPC radiation resistance and is significantly correlated with NPC recurrence. We further found that EGR1 upregulated PD-L1 expression at transcriptional level in a p38 MAPK dependent manner. Moreover, EGR1 participated in CD8+T cell mediated immune evasion in NPC radioresistant cells. We therefore propose a hypothesis that p38 MAPK/EGR1 axis induced PD-L1 expression promotes radiation resistance of NPC by enhancing immune evasion. This study aims to identify the key regulatory factors in p38 MAPK/EGR1/PD-L1 axis, especially PD-L1, as a new target to improve radiosensitivity of NPC, provide theoretical basis for PD-1/PD-L1 inhibitors plus radiotherapy in the treatment of NPC. Meanwhile, this study also provides the possibility for predicting the radiosensitivity of NPC. Citation Format: Dong-Fang Meng. p38 MAPK/EGR1/PD-L1 axis promotes radiation resistance of nasopharyngeal carcinoma by enhancing immune evasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5241.