Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 22 2 2023 04 30 163 171 EN Fateme Khani Chamani Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Mahdi Shabani Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Afshin Moradi Department of Pathology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Maedeh Alinejad Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran Seyed Amir Jalali Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran 2022 05 21 2023 02 15 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 RT 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 tumor microenvironment varied in different RT regimens with the same biologically effective dose. In this study, female BALB/c mice inoculated with CT26 tumor cells were irradiated with 3 different RT regimens using the same BED of 40 gray (Gy). These included ablative RT (1*15 Gy), hypo-fractionated RT (2*10 Gy), and conventional (Hyper-fractionated) RT (10*3 Gy). PD-L1 expression was analyzed with immunohistochemical staining on days 2 and 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 TME, so a combination of RT and immune checkpoint blockade could be clinically used in cancer patients. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/3534 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/3534/1941