Combining Radiation and Immunotherapy: A New Systemic Therapy for Solid Tumors?

Abstract

With the recent success of checkpoint inhibitors and other immune-modulating agents, there has been renewed interest in the combination of such agents with radiation. The biological premise behind such a strategy is that the tumor-antigen release achieved by localized radiation will promote specific tumor-targeting by the adaptive immune system, which can be augmented further by systemic immune-stimulating agents. In this manner, clinicians hope to induce a phenomenon known as the abscopal effect, whereby localized radiation results in immune-mediated tumor regression in disease sites well outside of the radiation field. In this Crossroads in Cancer Immunology article, we will present a comprehensive overview of the early clinical and pre-clinical evidence behind this approach.

Radiation therapy and the abscopal effect: a concept comes of age

“…A plausible explanation is that radiation treatments in different settings can be either immunosuppressive or immunostimulatory depending on tissue and tumor context, and the host anti-tumor immune response is often regulated through a tight network of opposing stimulatory and inhibitory signals (17,18). This study and other studies suggest that a permissive tumor/host environment and an appropriate set of immunomodulatory events at the proper timing may be necessary to trigger an abscopal response (19,20). We are only beginning to realize the complexity of these pathways and their interactions and find ways to enhance the anti-tumor immune response.…”

Rationale For Immune-Based Therapies in Merkel Polyomavirus-Positive and -Negative Merkel Cell Carcinomas

“…Radiation therapy has been shown to increase antigen presentation and to diversify the T-cell receptor repertoire of intratumoral CD8 T cells [99,100]. Preclinical models using targeted single-fraction radiation therapy (SFRT) indicate that SFRT enhances antitumor immunity more effectively than fractionated radiation [101].…”

Immune Checkpoint Inhibitors in the Treatment of Melanoma: From Basic Science to Clinical Application

“…In mice, antibody-mediated blockade of CTLA-4 induces complete tumor rejection and immunologic memory in several murine models of cancer (14). In addition, preclinical murine studies have shown that CTLA-4 blockade synergizes with radiation therapy (15), chemotherapy (16), molecularly targeted therapy (17), and tumor vaccination (18) to eradicate established tumors. Mechanistic studies in mice have shown that CTLA-4 blockade increases the ratio of effector T-cells to Foxp3+ Treg cells in tumors (19).…”