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Immunity. 2015 Apr 21;42(4):767-77. doi: 10.1016/j.immuni.2015.03.009. Epub 2015 Apr 14.

Complement is a central mediator of radiotherapy-induced tumor-specific immunity and clinical response.

Author information

1
Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
2
Department of Radio-Oncology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
3
Division Cell Biology II, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
4
ID Scientific IT Services, Swiss Federal Institute for Technology (ETH), Weinbergstrasse 11, 8092 Zurich, Switzerland.
5
Department of Dermatology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
6
Clinic of Oncology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland.
7
Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland. Electronic address: vandenbroek@immunology.uzh.ch.

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.

PMID:
25888260
DOI:
10.1016/j.immuni.2015.03.009
[Indexed for MEDLINE]
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