The antitumor immune response generated by fractionated radiation therapy may be limited by tumor cell adaptive resistance and can be circumvented by PD-L1 blockade.

Fractionated radiation therapy (RT) leads to adaptive changes in the tumor microenvironment that may limit the generation of an antitumor immune response. We demonstrated that fractionated RT led to increased tumor cell expression of programmed cell death ligand 1 (PD-L1) in response to CD8(+) T cell production of interferon gamma. Our data reveal that the efficacy of fractionated RT can be significantly improved through the generation of durable systemic immune responses when combined with concurrent, but not sequential, blockade of the PD-1/PD-L1 pathway.