Immune Priming of the Tumor Microenvironment by Radiation

Abstract

Ionizing irradiation can induce a multitude of alterations within the tumor microenvironment. Unlike targeted therapies, radiation delivered to the tumor bed can prompt phenotypic changes in both normal stromal and cancer cells, leading to molecular and physiological alterations within the tumor microenvironment. These environmental modulations directly influence the degree of immunogenicity of the tumor microenvironment and may ultimately affect tumor responsiveness to cancer immunotherapies. Here we review the preclinical evidence for tumor microenvironment-mediated immune suppression and how radiation can modulate immune properties within a tumor. We then discuss the therapeutic opportunities for combining radiation with molecular agents to enhance tumor immunogenicity and how this represents a potential exciting strategy to complement immunotherapies including immune checkpoint blockers in cancer treatment.

Keywords: abscopal effect; cancer immunotherapy; immune checkpoint inhibitor; immunogenic cell death; radioimmunotherapy; radiotherapy; tumor microenvironment.