Immune modulatory effects in Radiotherapy

Radiotherapy not only affects tumor tissue locally but activates the immune system. A release of tumor antigens, such as lethally damaged tumor cells and cellular debris, can be uptaken by circulating dendritic cells and other antigen-presenting cells, developing a tumor-specific immune reaction. These immune modulatory effects can be exploited to improve the efficacy of radiotherapy. In a number of preclinical studies the combination of immune therapy and radiotreatment has been shown to increase anti-tumor effects. Thereby, immune checkpoint inhibitors have been taking the center stage by acting as blockers to prevent immune exhaustion after radiotherapy. Without combinational immune treatment after radiotherapy, levels of programmed death-ligand 1 (PD-L1) increase in the tumor and tumor microenvironment. Antibodies for PD-L1 but also other immune suppressors, such as the cytotoxic T-lymphocyte-associated Protein 4, have been shown to boost the immune system in combination with radiotherapy.

Preclinical experiments run by our group reveal the effects of immune check point inhibitors such as PDL1 antibodies and DNA-damage repair inhibitors among others in combination with radiotherapy or in multimodal treatments. We apply the radiation dose in a clinical setting with fractionated radiotherapy (10 to 30 fractions) and compare the effects of different radiation qualities (photons, protons, and helium, carbon, or oxygen ions) to find the most effective treatment arrangement.

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