Aiming the Immune System to Improve the Antitumor Efficacy of Radiation Therapy

Abstract

Radiation therapy (RT) has historically been the most common approach used to achieve local tumor control in cancer patients. However, emerging evidences over the last decades suggest an important role for RT in modulating or amplifying the antitumor immune response upon induction of cancer cell death through its direct cytocidal effect. RT alters multiple components of the tumor microenvironment which affect both the immune cell phenotype and function as well as the interactions between tumor and the immune system. Despite the documented immunostimulatory effects, RT alone rarely induces effective antitumor immunity resulting in systemic tumor rejection. RT can also reinforce immunosuppressive mechanisms within the tumor microenvironment, which negatively impacts on the tumor response to RT. Preclinical and clinical data show that combination RT and immunotherapy can elicit powerful antitumor efficacy through either strengthening the immune activation or counteracting immune suppression. In this review, we summarize the immunological changes in the tumor microenvironment upon exposure to radiation. We also highlight radiation triggered molecular and cellular pathways that may contribute to immune evasion and tumor recurrence. Rational and optimized combination of RT and immunotherapy to achieve synergistic antitumor activities for systemic eradication of cancer cells and development of durable antitumor immunity will also be discussed.