Radiotherapy (RT) is still one of the standard cancer therapies, with up to two third of all cancer patients with solid tumors being irradiated in the course of their disease. The aim of using ionizing radiation in fractionated treatment schedules was always to achieve local tumor control by inducing DNA damage which can be repaired by surrounding normal tissue but leads to cell death in tumor cells. Meanwhile, it is known that RT also has immunological effects reshaping the tumor microenvironment. Nevertheless, RT alone often fails to elicit potent antitumor immune responses as these effects can be immunostimulatory as well as immunosuppressive. Here, we discuss how immunotherapies can be exploited in combined therapies to boost RT-induced antitumor immune responses or to counteract preexisting and RT-mediated immunosuppression to improve local and systemic tumor control. Furthermore, we highlight some parameters of radioimmunotherapies (RITs) which are under investigation for potential optimizations and how RIT approaches are tested in first phases II and III trials. Finally, we discuss how RT might affect normal and cancer stem cells.

Radon treatment is used as an established therapy option in chronic painful inflammatory diseases. While analgesic effects are well described, little is known about the underlying molecular effects. Among the suspected mechanisms are modulations of the anti-oxidative and the immune system. Therefore, we aimed for the first time to examine the beneficial effects of radon exposure on clinical outcome as well as the underlying mechanisms by utilizing a holistic approach in a controlled environment of a radon chamber with an animal model: K/BxN serum-induced arthritic mice as well as isolated cells were exposed to sham or radon irradiation. The effects on the anti-oxidative and the immune system were analyzed by flow-cytometry, qPCR or ELISA. We found a significantly improved clinical disease progression score in the mice, alongside significant increase of peripheral blood B cells and IL-5. No significant alterations were visible in the anti-oxidative system or regarding cell death. We conclude that neither cell death nor anti-oxidative systems are responsible for the beneficial effects of radon exposure in our preclinical model. Rather, radon slightly affects the immune system. However, more research is still needed in order to fully understand radon-mediated effects and to carry out reasonable risk-benefit considerations.