The Immunoregulatory Potential of Particle Radiation in Cancer Therapy

Abstract

Cancer treatment, today, consists of surgery, chemotherapy, radiation, and most recently immunotherapy. Combination immunotherapy-radiotherapy (CIR) has experienced a surge in public attention due to numerous clinical publications outlining the reduction or elimination of metastatic disease, following treatment with specifically ipilimumab and radiotherapy. The mechanism behind CIR, however, remains unclear, though it is hypothesized that radiation transforms the tumor into an in situ vaccine which immunotherapy modulates into a larger immune response. To date, the majority of attention has focused on rotating out immunotherapeutics with conventional radiation; however, the unique biological and physical benefits of particle irradiation may prove superior in generation of systemic effect. Here, we review recent advances in CIR, with a particular focus on the usage of charged particles to induce or enhance response to cancerous disease.

Keywords: abscopal; carbon; immunotherapy; particle therapy; proton.

Figure 1

Comparison of the dose distribution for carbon ion and X-rays. Panel (A) shows the physical profile of a single peak compared to a typical photon irradiation; in panel (B), the resulting profile of a biologically effective dose obtained with a Spread-Out Bragg Peak. Courtesy of Dr. Scifoni, Trento Institute for Fundamental Physics and Applications (TIFPA-INFN).

Figure 2

Radiation increases major histocompatibility complex I and enhances calreticulin (CRT) translocation and ATP-high mobility group box-1 (HMGB1) release. Those signals are fundamental to activate dendritic cells (DC). Activated DC increase their mobility and move to the lymph nodes where they activate T-cells. The increase of prostaglandin E2 (PGE2) and TGFβ could yet be counterproductive, increasing the population of myeloid-derived suppressor cells (MDSC) and Treg cells responsible for immunosuppression.