Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice

摘要: High-dose ionizing irradiation (IR) results in direct tumor cell death and augments tumor-specific immunity, which enhances control both locally distantly. Unfortunately, local relapses often occur following IR treatment, indicating that IR-induced responses are inadequate to maintain antitumor immunity. Therapeutic blockade of the T negative regulator programmed death–ligand 1 (PD-L1, also called B7-H1) can enhance effector function when PD-L1 is expressed chronically inflamed tissues tumors. Here, we demonstrate was upregulated microenvironment after IR. Administration anti–PD-L1 enhanced efficacy through a cytotoxic cell–dependent mechanism. Concomitant with IR-mediated regression, observed synergistically reduced accumulation tumor-infiltrating myeloid-derived suppressor cells (MDSCs), suppress alter immune microenvironment. Furthermore, activation combination therapy mediated reduction MDSCs tumors actions TNF. Our data provide evidence for close interaction between IR, cells, PD-L1/PD-1 axis establish basis rational design modulators radiotherapy.