α-PD-L1 mAb enhances the abscopal effect of hypo-fractionated radiation by attenuating PD-L1 expression and inducing CD8 + T-cell infiltration

Abstract

Aim: We investigated a promising cooperative combination of radiotherapy (RT) and programmed death ligand 1 (PD-L1) monoclonal antibodies (mAb) in both local and abscopal tumors. Materials & methods: C57BL/6 mice were randomly grouped and received RT, α-PD-L1 mAb or combination therapy 13 days after implantation of Lewis lung carcinoma cells. Flow cytometry and immunohistochemistry analyses demonstrated CD8 + T-cell infiltration and PD-L1 expression in tumor issue. Cytometric bead arrays were used to examine cytokine levels. Results: Our studies revealed that administration of 8 Gy × 3 F with α-PD-L1 mAb promoted both local and distant control. Only local hypofractionated RT enhanced CD8 + T-cell infiltration with increased PD-L1 expression at distant foci, which might occur via serum IFN-γ modulation. Addition of α-PD-L1 mAb reduced PD-L1 expression and further increased CD8 + T-cell infiltration. Conclusion: We identified a novel mechanism through which combination therapy enhanced the abscopal effect.