Radiation and the immune system: current knowledge and future perspectives

For long, high dose ionizing radiation was considered as a net immune suppressing agent, as shown, among others, by the exquisite radiosensitivity of the lymphoid system to radiation-induced cell killing. However, recent advances in radiobiology and immunology have made this picture more complex. For example, the recognition that radiation-induced bystander effects, share common mediators with various immunological signalling processes, suggests that they are at least partly immune mediated. These effects are elicited by both low and high doses of radiation exposure, including out-of-field effects occurring during radiotherapy. Another milestone was the finding, in the field of onco-immunology, that local tumor irradiation can modulate the immunogenicity of tumor cells and the anti-tumor immune responsiveness both locally, in the tumor microenvironment, and at the systemic level. These observations paved the way for studies exploring optimal combinations of radiotherapy and immunotherapy in order to achieve a synergistic effect to eradicate tumors. However, not all interactions between radiation and the immune system are beneficial, as it was recognized that many of radiation-induced late side effects are also of immune and inflammatory nature. Currently perhaps the most studied field of research in radiation biology is focused around the biological effects of low doses, where many of the observed pathophysiological endpoints are due to mechanisms other than direct radiation-induced cell killing. Accumulating evidences indicate different mechanisms of immune modulation at low doses and at high, therapeutic doses. Finally, it must not be forgotten that the interactions between the ionizing radiations and the immune system are bi-directional, and activation of the immune system also influences the outcome of radiation exposure, as shown by studies addressing the modulatory effects of cytokines and TLRs ligands on the in-vivo response to radiation.

In summary, we are currently facing the emergence of radioimmunobiology, a new interdisciplinary field addressing the interactions between ionizing radiations and the immune system. The impact of studies in this field already led to a change in paradigm, and there is no doubt that further studies in radioimmunobiology will lead to direct clinical applications within a relatively short term. The present Frontiers topic intends to explore the interdisciplinary nature of radioimmunobiology and welcomes contributions in the form of reviews, mini-reviews and original articles from the radiobiology, immunology, molecular and cellular biology community as well as from different clinical sciences in the following (but not restricted to) topics:

- Basic interactions between ionizing radiation and the immune system
- Radio-onco-immunology and combined radio and immunotherapy approaches in oncology
- Immune modulatory effects of low doses, basic mechanisms, potential therapeutic applications
- Radiation-induced chronic inflammation and its consequences in various organs
- Immune-related biomarkers of radiation exposure