Radiotherapy activates autophagy to increase CD8+ T cell infiltration by modulating major histocompatibility complex class-I expression in non-small cell lung cancer

Abstract

Objective: Radiotherapy is reported to enhance immune responses in cancer, but appropriate doses and mechanisms remain to be investigated. This study explored whether autophagy is involved in the regulation of major histocompatibility complex class I (MHC-I) expression and CD8+ T cell infiltration at different radiation doses. Methods: Non-small cell lung cancer (NSCLC) cell lines A549 and H1975 were exposed to different doses of radiation. The levels of autophagy and MHC-I expression were examined 6 hours after irradiation. The effects of the autophagy inhibitor chloroquine (CQ) on MHC-I expression were also investigated, as well as the relationship between autophagy and MHC-1 expression. Pathological specimens from 69 NSCLC patients were collected, and immunohistochemistry was used to detect MHC-1 expression and CD8+ T cell infiltration in tumors. Results: Irradiation induced autophagy and MHC-I expression during a single radiation dose from 2 to 20 Gy in a dose-dependent manner. CQ downregulated MHC-I expression. Immunohistochemistry indicated that MHC-I levels were positively correlated with the infiltration of CD8+ T cells in NSCLC cells (R2 = 0.713). Conclusions: Autophagy induced MHC-I expression and increased CD8+ T cell infiltration. A single radiation dose of 20 Gy induced the strongest CD8+ T cell infiltration.