Evaluation of molecular-level changes of Programmed cell Death Ligand-1 after radiotherapy in a BALB/c CT26 colorectal mouse tumor model

Abstract

The effects of radiation therapy (RT) for cancer can be systemic and partially mediated by the immune system. However, radiation alone is unlikely to transform an immunosuppressive environment into an immunostimulatory one. Therefore, an effective combination of radiation therapy and immunotherapy may provide a new more efficient treatment approach. Here we investigated how the expression of programmed cell death-ligand 1 (PD-L1) in the microenvironment of the tumor varied in different RT regimens with the same Biologically Effective Dose (BED). In this study, female BALB/c mice inoculated with CT26 tumor cells were irradiated with three different RT regimens using the same Biologically Effective Dose (BED) of 40 Gray (Gy). These included Ablative RT (1*15 Gy), Hypo-fractionated RT (2*10 Gy), and Conventional RT (10*3 Gy). PD-L1 expression was analyzed with immunohistochemical staining on days 2, 20, and when the size of tumors had reached 2 cm2 after RT. All treated groups expressed PD-L1, but the group receiving single ablative high dose RT showed higher expression compared to the other groups. No significant differences in PD-L1 expression were observed at different times in the same group. These findings showed that different regimens of RT have different effects on the tumor microenvironment (TME), so a combination of RT and immune checkpoint blockade could be clinically used in cancer patients.