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Immune effects of radiotherapy and combinations of immunotherapy and radiotherapy have been a research focus for biologists and clinicians over the last decade. Effective anti-tumor immunity requires complex processes starting with an activation of the innate immune system through danger signals in the tumor, which leads to effective activation of antigen presenting cells. Those activated cells travel to the tumor draining lymph node, where they prime antigen specific T cells (helper T cells and cytotoxic T cells). There are two main “polarizations” of such a T cell activation, that show a marked difference in eliciting anti-tumor immune responses. Activated T cells travel from the draining lymph node to the blood stream and thus through the whole body. Upon recognizing the antigen they had been primed for in the lymph node they start proliferating and destroying tumor cells. Tumors are very effective in counter-acting this immune destruction (otherwise they would not grow to clinically apparent tumors) through multiple mechanisms, such as upregulation of immune checkpoints, creating a highly immunosuppressive microenvironment or downregulation of target molecules on their cell surface.



Irradiation of tumors alters the immune microenvironment of the tumor depending on tumor features (e.g. entity, metastasis versus primary tumor), radiation dose and fractionation as well as concomitant or sequential systemic therapies and can either facilitate anti-tumor immune responses or aggravate tumor immune suppression. While most combinatorial approaches in the clinic use immune-checkpoint inhibition, there is a plethora of different immunotherapy classes (e.g. cytokine based approaches, cellular therapies and bispecific antibodies), all of which might differ in the radiotherapy regimens and schedules to best be combined with.



Emerging questions during the last years started to connect this field of research to topics in physics. The perspective of inducing „immunogeneic cell death“ (specific cell death modes leading to a release of danger signals and stimulation of anti-cancer immunity) suggested best immune responses with high single dose irradiation. However, preclinical evidence suggested best abscopal effects (anti tumor immune effects outside the irradiated volume) for hypofractionated regimens in a murine model of breast cancer treated with immune checkpoint inhibition and irradiation. As immune cells, especially circulating lymphocytes, are highly radiosensitive, the role of low dose regions with the use of intensity modulated radiotherapy has been questioned concerning anti-tumor immune responses. Also based on preclinical findings, a strong suppressive effect on anti-tumor immunity was reported for irradiation of tumor draining lymph nodes leading to the hypothesis of „nodal sparing radiotherapy“. As many immune cells are circulating in the blood and stem from bone marrow, these structures might be integrated in radiotherapy planning as „immune related organs at risk“.



This teaching lecture will give an overview of the basic mechanisms of cancer immunity and cancer immunotherapy. In addition, immune effects of radiotherapy and current conceptual discussions about radiotherapy planning in the context of tumor immunology will be introduced.