Immune effects of high dose radiation treatment: Implications of ionizing radiation on the development of bystander and abscopal effects

Abstract

Tumors grow progressively when they escape from immune surveillance. Cancer progression is mainly driven by the expansion of tumor cells, but tumor microenvironment and anti-tumor immunity may also play a role. Ionizing radiation therapy (RT), either alone or in combination with additional immune stimulators, can render cancer cells visible to the immune system. In addition to the direct effects of radiation, the ensuing immune response promotes the expression of inflammatory and immunostimulatory mediators, which act on neighboring, non-irradiated, cells. Bystander effects induced by radiation are characterized by biological responses, which are observed in non-irradiated cells that are in the vicinity of irradiated cells. Bystander effects are mediated via cell-to-cell gap junctions or through secreted, diffusible signaling molecules into the local milieu. After treatment with localized radiation, systemic effects in non-irradiated area (out-offield) may also occur. These effects are named abscopal effects and appear to be immune mediated, particularly by adaptive immunity. It has been suggested that a high single dose of RT may induce an immune response that leads to the priming of antigen-specific dendritic cells (DCs). The targeted intraoperative radiotherapy (TARGIT) method, using INTRABEAM®, could reduce tumor recurrence, modifying the wound microenvironment, and eradicating residual tumor cells when applied immediately after surgery procedure.