Radiation-induced change of PD-1/PD-L1 immune checkpoint in mouse colon cancer models

Abstract

Abstract Background Radiotherapy (RT), a major part of anti-cancer treatment, directly kills tumor cells, and subsequent anti-tumor immune responses are up-regulated. However, immunologic impacts of RT on PD-1/PD-L1 immune checkpoint activity has not been much investigated. This study evaluated RT-induced alterations of the PD-1/PD-L1 checkpoint molecules based on murine colon carcinoma models. Methods CT26 colon carcinoma cell line was subcutaneously inoculated on the right hind leg of BALB/c mice. Based on tumor growth curves after irradiation of 15 Gy x 1 fx or 5 Gy x 3 fx, mouse tumors were surgically resected on 4 different time points: “Pre-RT”, non-irradiated status just prior to initiation of RT; “Early”, the early phase of RT response; “Nadir”, representing minimal tumor volume; and “Regrowth”, with regrown tumors after RT. PD-L1 expression on tumor cells, PD-1 expression on tumor-infiltrating CD4+ and CD8+ T cells, and proportions of tumor-infiltrating CD4+ and CD8+ T cell populations were estimated using flow cytometry analysis. Results PD-L1 expression on mouse tumor cells surged within a few days after completion of RT, followed by abrupt decreases on the “Nadir” and “Regrowth” phases (P Conclusions This study verified radiation-induced immunologic shift and dynamic change of the PD-1/PD-L1 checkpoint activity and tumor-infiltrating lymphocytes. The change was maximal at the early phase of RT response, which highlights the need of concurrent combinatory strategy of PD-L1 blockade and RT. Legal entity responsible for the study The author. Funding National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science, ICT & Future Planning) (NRF-2019R1C1C1007994). Disclosure The author has declared no conflicts of interest.