Synergistic effects of anti-PDL-1 with ablative radiation comparing to other regimens with same biological effect dose based on different immunogenic response

Introduction Irradiation can induce multiple inhibitory and stimulatory effects on the immune system. In recent studies, it has been noted that administration of radiation with various doses and fractionation plans may influence on immune responses in microenvironment of tumor. But in radiobiology, the Biologically Effective Dose (BED) formula has been designed for calculating isoeffect doses in different regimens of daily clinical practice. In other words, BED has also been used to predict the effects of fractionation schedules on tumor cells. Methods In our study, three different regimens with BEDs of 40 gray (Gy) were analyzed in BALB/c mice. These included conventional fractionated radiotherapy (RT) (3Gyx10), high-dose hypofractionated RT (10Gyx2), and single ablative high-dose RT (15Gyx1). Results As BED predicts, all three similarly decreased tumor volumes and increased survival times relative to controls, but after high dose exposure in ablative group, the expression of IFN Upsilon was increased following high infiltration of CD8 cells into the tumor microenvironment. When anti-PDL-1 was combined with RT, single ablative high-dose radiation enhanced antitumor activity by increasing IFN Upsilon in tumors and CD8(+) tumor-infiltrating lymphocytes; as a result, this combining therapy had enhanced antitumor activity and lead to control tumor volume effectively and improve significantly survival rate and finally the recurrence of tumor was not observed. Conclusion Results show distinct radiation doses and fractionation schemes with same BED have different immunogenic response and these findings can provide data helping to design regimens of radiation combined with immune checkpoint blockers (ICBs).