Immune modulatory properties of radiotherapy

Abstract

Radiotherapy (RT) is a common treatment for cancer and about 60% of all cancer patients will receive it during their course of illness. RT primarily aims to achieve local tumor control. The induction of DNA damage by reactive oxygen species (ROS), tumor cell death and the modulation of the tumor microenvironment are the main effects of ionizing irradiation to reduce tumor masses, but also to modulate the immune system. RT might thereby act as an in situ cancer vaccine under certain microenvironmental conditions. However, RT also fosters the upregulation of immune suppressive molecules such as immune checkpoint molecules.

The presentation will focus on how local irradiation changes the tumor cell phenotype and the tumor microenvironment and consecutively does impact on local and systemic changes in immune cell compositions. In particular the impact of ROS, danger signals and cytokines on it will be outlined. The dynamics of immune changes, the radiosensitivity of distinct immune cells as well as biological basis for reasonable combination of RT with immune stimulation will be discussed in detail, as well as how radiation-induced immune suppression can be overcome. Based on the pre-clinical knowledge, innovative clinical study concepts of radio-immune treatments will be presented.