Background: Traditional concepts of radiobiology model the direct radiation-induced cellular cytotoxicity but are not focused on late and sustained effects of radiation. Recent experimental data show the close involvement of immunological processes.
Methods: Based on systematic PubMed searches, experimental data on immunological radiation effects are summarized and analyzed in a non-quantitative descriptive manner to provide a translational perspective on the immuno-modulatory impact of radiation in cancer.
Results: Novel experimental findings document that sustained radiation effects are ultimately mediated through systemic factors such as cytotoxic CD8+ T cells and involve a local immuno-stimulation. Increased tumor infiltration of CD8+ T cell is a prerequisite for long-term radiation effects. CD8+ T cell depletion induces radio-resistance in experimental tumors. The proposed sequence of events involves radiation-damaged cells that release HMGB1, which activates macrophages via TLR4 to a local immuno-stimulation via TNF, which contributes to maturation of DCs. The mature DCs migrate to lymph nodes where they trigger effective CD8+ T cell responses. Radiation effects are boosted, when the physiological self-terminating negative feedback of immune reactions is antagonised via blocking of TGF-β or via checkpoint inhibition with involvement of CD8+ T cells as common denominator.
Conclusion: The concept of immuno-radiobiology emphasizes the necessity for a functional integrity of APCs and T cells for the long-term effects of radiotherapy. Local irradiation at higher doses induces tumor infiltration of CD8+ T cells, which can be boosted by immunotherapy. More systematic research is warranted to better understand the immunological effects of escalating radiation doses.
Keywords: CD8+ T cells; Immuno-radiobiology; Onco-immunology; Radiobiology; Radiosurgery; Radiotherapy.
Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.