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. 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 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 and are immune-related. 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. This Research Topic brings together 23 articles and aims to give an overview of the complex and very often contradictory nature of the interactions between ionizing radiation and the immune system. Due to its increasing penetrance in the population both through medical diagnostic or environmental sources or during cosmic travel low dose ionizing radiation exposure is becoming a major epidemiological concern world-wide. Several of the articles within the Research Topic specifically address potential long-term health consequences and the underlying mechanisms of low dose radiation exposure. A major intention of the Editors was also to draw the attention of the non-radiobiological scientific community on the fact that ionizing radiation is by far more than purely an immune suppressing agent.

This book reevaluates the health risks of ionizing radiation in light of data that have become available since the 1980 report on this subject was published. The data include new, much more reliable dose estimates for the A-bomb survivors, the results of an additional 14 years of follow-up of the survivors for cancer mortality, recent results of follow-up studies of persons irradiated for medical purposes, and results of relevant experiments with laboratory animals and cultured cells. It analyzes the data in terms of risk estimates for specific organs in relation to dose and time after exposure, and compares radiation effects between Japanese and Western populations.

Numerous developments in molecular biology have led to an explosive growth in the knowledge underlying mechanisms of carcinogenesis, cell signalling, tumor progression and development of metastasis. However, cure of cancer is still hampered by the inherited capacity of tumors to become resistant to standard therapies, to metastasize from their initial location and to proliferate in other tissue compartments. Radiotherapy is one of the main treatment modalities to achieve locoregional tumor control. However, the treatment of distant metastases further remains to be a challenge. In this special topic we are interested to elucidate immunological aspects which are initiated and affected by radiotherapy. We also aim to describe the development of innovative immunological strategies from a preclinical stage to clinical application which could be combined with standard radiotherapeutic approaches. A special interest will also deal with the effects of radiotherapy on tumor initiating cells as well as on the tumor microenvironment. Last but not least the effects of different irradiation sources and qualities such as photones, protones and heavy ions will be analyzed with respect to immunological outcome.

Ionizing Radiation and the Immune Response, Volume 376, Part A reviews the latest updates on the immune response induced by ionizing radiations. Sections discuss NK functions in radio-induced immune response, TRT and immune response, Radio-induced immune response and lipid metabolism, Effect of protons and heavy ions on immune response, Effect of flashtherapy and mini beam on immune response, Radio-induced lymphopenia, CT to potentiate radio-induced immune response, Impact of RT on healthy tissues (inflammation), Radio-induced macrophagic response, To use nanoparticles and ionizing radiations to modulate immune response: opinion of the chemist, biologist and clinician, and more. Additional sections touch on the Effect of low dose radiation on radio-induced immune response, Role of Dendritic cells in radiation-induced immune response, Relationship between the tumor microenvironment and the efficacy of the radiotherapy/immunotherapy combination+A23, and Biomarkers of radiation induced response to optimize radio-immunotherapy combination. Covers the latest insights on the biological and physical parameters that modulate radio-induced immune response Provides an accurate review by selected experts of the impact on the immune response of new techniques delivering ionizing radiations Presents valuable information to clinicians to optimize radiotherapy and immunotherapy combinations

Ionizing Radiation and the Immune Response, Part B, Volume 378 reviews the latest knowledge on the immune response induced by ionizing radiations. Specific chapters in this new release include NK functions in radio-induced immune response, TRT and immune response, Radio-induced immune response and lipid metabolism, Effect of protons and heavy ions on immune response, Effect of flash therapy and mini beam on immune response, Radio-induced lymphopenia, CT to potentiate radio-induced immune response, Impact of RT on healthy tissues (inflammation), Radio-induced macrophagic response, To use nanoparticles and ionizing radiations to modulate immune response: opinion of the chemist, biologist and clinician, and much more. Other sections cover the Role of Dendritic cells in radiation-induced immune response, the Relationship between the tumor microenvironment and the efficacy of the radiotherapy/immunotherapy combination, and Biomarkers of radiation induced response to optimize radio-immunotherapy combination. Covers the latest insights about the biological parameters modulating radio-induced immune response Provides an accurate review by selected experts of the impact on the immune response of radio-enhancer nanoparticles or chemotherapy targeting immunosuppressive immune cells Presents valuable information to clinicians to optimize radiotherapy and immunotherapy combinations