Modulation of inflammation by low and high doses of ionizing radiation: Implications for benign and malign diseases. Issue 2 (28th November 2015)

• Record Type: Journal Article
• Authors: Frey, Benjamin; Hehlgans, Stephanie; Rödel, Franz; Gaipl, Udo S.
• Is Part Of: Cancer letters. Volume 368:Issue 2(2016)
• Page Start: 230
• Page End: 237
• Publication Date: 2015-11-28
• Subjects: Inflammation -- Ionizing radiation -- Immune biomarkers -- Tumor-infiltrating lymphocytes -- Tumor-associated macrophages -- Low-dose radiation therapy; Cancer -- Periodicals; Neoplasms -- Periodicals; Cancer -- Périodiques; Electronic journals; 616.994
• DOI: 10.1016/j.canlet.2015.04.010
• Languages: English
• ISSNs: 0304-3835

Abstract

Highlights: Inflammation is modulated by ionizing radiation. Ionizing radiation might initiate inflammatory reactions and thereby contribute to tumor development. Ionizing radiation, especially combined with additional immune stimulation, fosters induction of immunogenic tumor cell death. Immunological biomarkers for prediction and prognosis of cancer disease will further ameliorate multimodal cancer therapies. Ionizing radiation at low doses attenuates established inflammatory diseases. Abstract: Inflammation is a homeostatic mechanism aiming to maintain tissue integrity. The underlying immunological mechanisms and the interrelationship between ionizing radiation and inflammation are complex and multifactorial on cellular and chemical levels. On the one hand, radiation with single doses exceeding 1 Gy might initiate inflammatory reactions and thereby impact on tumor development. On the other hand, radiation is capable of attenuating an established inflammatory process, which is clinically used for the treatment of inflammatory and degenerative diseases with low-dose radiotherapy (single dose <1 Gy). At higher doses, ionizing radiation, especially in combination with additional immune stimulation, fosters the induction of immunogenic forms of tumor cell death and shifts the tumor microenvironment as well as the infiltration of immune cells from an anti- to a pro-inflammatory state. Distinct tumor infiltrating immune cells predict the response to radiochemotherapy in a multitude of tumor entities. While a high tumor infiltration of these adaptive immune cells mostly predicts a favorable disease outcome, a high infiltration of tumor-associated macrophages predicts an unfavorable response. Pro-inflammatory events should dominate over anti-inflammatory ones in this scenario. This review focuses on how ionizing radiation modulates inflammatory events in benign inflammatory and in malign diseases. A special focus is set on the role of tumor infiltrating lymphocytes and macrophages as biomarkers to predict treatment response and anti-tumor immunity and on mechanisms implicated in the anti-inflammatory effects of low-dose radiation therapy.