Abstract
Radiotherapy induces DNA damage and cell death, but recent data suggest that concomitant immune stimulation is an integral part of the therapeutic action of ionizing radiation. It is poorly understood how radiotherapy supports tumor-specific immunity. Here we report that radiotherapy induced tumor cell death and transiently activated complement both in murine and human tumors. The local production of pro-inflammatory anaphylatoxins C3a and C5a was crucial to the tumor response to radiotherapy and concomitant stimulation of tumor-specific immunity. Dexamethasone, a drug frequently given during radiotherapy, limited complement activation and the anti-tumor effects of the immune system. Overall, our findings indicate that anaphylatoxins are key players in radiotherapy-induced tumor-specific immunity and the ensuing clinical responses.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antineoplastic Agents, Hormonal / pharmacology
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Complement Activation
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Complement C3a / genetics
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Complement C3a / immunology*
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Complement C5a / genetics
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Complement C5a / immunology*
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Dexamethasone / pharmacology
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Gamma Rays
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Gene Expression Regulation, Neoplastic / immunology*
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Humans
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Immunity, Innate / drug effects
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Immunity, Innate / radiation effects*
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Melanoma, Experimental / genetics
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Melanoma, Experimental / immunology*
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Melanoma, Experimental / pathology
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Melanoma, Experimental / radiotherapy
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Complement / genetics
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Receptors, Complement / immunology
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Signal Transduction
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Skin Neoplasms / genetics
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Skin Neoplasms / immunology*
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Skin Neoplasms / pathology
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Skin Neoplasms / radiotherapy
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Tumor Burden / radiation effects
Substances
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Antineoplastic Agents, Hormonal
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Receptors, Complement
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Dexamethasone
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Complement C3a
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Complement C5a