Immunity (Cambridge, Mass.), 2015-04, Vol.42 (4), p.767-777
2015
Details
- Autor(en) / Beteiligte
- Titel
- Complement Is a Central Mediator of Radiotherapy-Induced Tumor-Specific Immunity and Clinical Response
- Ist Teil von
- Immunity (Cambridge, Mass.), 2015-04, Vol.42 (4), p.767-777
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2015
- Link zum Volltext
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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. [Display omitted] •RT induces local complement activation in mice and humans•RT-mediated cell death and necrosis activates complement•C3a and C5a accumulate in the tumor and promote tumor-specific immunity•Dexamethasone inhibits complement activation and reduces efficacy of RT Anaphylatoxins are produced upon complement activation and are well-known pro-inflammatory molecules. van den Broek and colleagues demonstrate that anaphylatoxins are produced within a tumor after radiotherapy by immune cells, support tumor-specific immunity, and are essential to therapeutic efficacy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1074-7613eISSN: 1097-4180DOI: 10.1016/j.immuni.2015.03.009Titel-ID: cdi_proquest_miscellaneous_1732833239
- Format
- –
- Schlagworte
- Animals, Antineoplastic Agents, Hormonal - pharmacology, Biopsy, Cancer, Colleges & universities, Complement Activation, Complement C3a - genetics, Complement C3a - immunology, Complement C5a - genetics, Complement C5a - immunology, Dexamethasone - pharmacology, Drug dosages, Experiments, Gamma Rays, Gene Expression Regulation, Neoplastic - immunology, Humans, Immune system, Immunity, Innate - drug effects, Immunity, Innate - radiation effects, Immunology, Medical research, Melanoma, Melanoma, Experimental - genetics, Melanoma, Experimental - immunology, Melanoma, Experimental - pathology, Melanoma, Experimental - radiotherapy, Mice, Mice, Inbred C57BL, Mice, Knockout, Radiation therapy, Receptors, Complement - genetics, Receptors, Complement - immunology, Signal Transduction, Skin Neoplasms - genetics, Skin Neoplasms - immunology, Skin Neoplasms - pathology, Skin Neoplasms - radiotherapy, Tumor Burden - radiation effects, Tumors