دورية أكاديمية
Priming anti-tumor immunity by radiotherapy: Dying tumor cell-derived DAMPs trigger endothelial cell activation and recruitment of myeloid cells
| العنوان: | Priming anti-tumor immunity by radiotherapy: Dying tumor cell-derived DAMPs trigger endothelial cell activation and recruitment of myeloid cells |
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| المؤلفون: | Julia Krombach, Roman Hennel, Nikko Brix, Michael Orth, Ulrike Schoetz, Anne Ernst, Jessica Schuster, Gabriele Zuchtriegel, Christoph A. Reichel, Susanne Bierschenk, Markus Sperandio, Thomas Vogl, Steffen Unkel, Claus Belka, Kirsten Lauber |
| المصدر: | OncoImmunology, Vol 8, Iss 1 (2019) |
| بيانات النشر: | Taylor & Francis Group, 2019. |
| سنة النشر: | 2019 |
| المجموعة: | LCC:Immunologic diseases. Allergy LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens |
| مصطلحات موضوعية: | radiotherapy, anti-tumor immunity, abscopal effects of radiotherapy, damps, endothelial cell activation, apc recruitment, cancer immunotherapy, Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282 |
| الوصف: | The major goal of radiotherapy is the induction of tumor cell death. Additionally, radiotherapy can function as in situ cancer vaccination by exposing tumor antigens and providing adjuvants for anti-tumor immune priming. In this regard, the mode of tumor cell death and the repertoire of released damage-associated molecular patterns (DAMPs) are crucial. However, optimal dosing and fractionation of radiotherapy remain controversial. Here, we examined the initial steps of anti-tumor immune priming by different radiation regimens (20 Gy, 4 × 2 Gy, 2 Gy, 0 Gy) with cell lines of triple-negative breast cancer in vitro and in vivo. Previously, we have shown that especially high single doses (20 Gy) induce a delayed type of primary necrosis with characteristics of mitotic catastrophe and plasma membrane disintegration. Now, we provide evidence that protein DAMPs released by these dying cells stimulate sequential recruitment of neutrophils and monocytes in vivo. Key players in this regard appear to be endothelial cells revealing a distinct state of activation upon exposure to supernatants of irradiated tumor cells as characterized by high surface expression of adhesion molecules and production of a discrete cytokine/chemokine pattern. Furthermore, irradiated tumor cell-derived protein DAMPs enforced differentiation and maturation of dendritic cells as hallmarked by upregulation of co-stimulatory molecules and improved T cell-priming. Consistently, a recurring pattern was observed: The strongest effects were detected with 20 Gy-irradiated cells. Obviously, the initial steps of radiotherapy-induced anti-tumor immune priming are preferentially triggered by high single doses – at least in models of triple-negative breast cancer. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2162-402X 2162402X |
| العلاقة: | https://doaj.org/toc/2162-402XTest |
| DOI: | 10.1080/2162402X.2018.1523097 |
| الوصول الحر: | https://doaj.org/article/90e51b19a2dc42efa094bb4b946d8d53Test |
| رقم الانضمام: | edsdoj.90e51b19a2dc42efa094bb4b946d8d53 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2162402X |
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| DOI: | 10.1080/2162402X.2018.1523097 |