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Immunomodulation by ionizing radiation—impact for design of radio‐immunotherapies and for treatment of inflammatory diseases
Author(s) -
Frey Benjamin,
Rückert Michael,
Deloch Lisa,
Rühle Paul F.,
Derer Anja,
Fietkau Rainer,
Gaipl Udo S.
Publication year - 2017
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/imr.12572
Subject(s) - immune system , cancer research , cancer , inflammation , immunotherapy , immunology , acquired immune system , immunogenic cell death , adjuvant , radiation therapy , medicine , tumor microenvironment , ionizing radiation , biology , irradiation , physics , nuclear physics
Summary Ionizing radiation is often regarded as an element of danger. But, danger responses on the cellular and molecular level are often beneficial with regard to the induction of anti‐tumor immunity and for amelioration of inflammation. We outline how in dependence of radiation dose and fraction, radiation itself—and especially in combination with immune modulators—impacts on the innate and adaptive immune system. Focus is set on radiation‐induced changes of the tumor cell phenotype and the cellular microenvironment including immunogenic cancer cell death. Mechanisms how anti‐tumor immune responses are triggered by radiotherapy in combination with hyperthermia, inhibition of apoptosis, the adjuvant AnnexinA5, or vaccination with high hydrostatic pressure‐killed autologous tumor cells are discussed. Building on this, feasible multimodal radio‐immunotherapy concepts are reviewed including overcoming immune suppression by immune checkpoint inhibitors and by targeting TGF ‐β. Since radiation‐induced tissue damage, inflammation, and anti‐tumor immune responses are interconnected, the impact of lower doses of radiation on amelioration of inflammation is outlined. Closely meshed immune monitoring concepts based on the liquid biopsy blood are suggested for prognosis and prediction of cancer and non‐cancer inflammatory diseases. Finally, challenges and visions for the design of cancer radio‐immunotherapies and for treatment of benign inflammatory diseases are given.