Tumour ischaemia by interferon-γ resembles physiological blood vessel regression
| Autor: | Thomas Kammertoens, Giannino Patone, Andranik Ivanov, Anna Szymborska, Séverine Kunz, Christian Friese, Norbert Hubner, Ana Textor, Dieter Beule, Holger Gerhardt, Ainhoa Arina, Marcus Fruttiger, Hans Joerg Fehling, Daniel Sommermeyer, Michael Lohoff, Hans Schreiber, Christian Idel, Michael Rothe, Boris Engels, Matthias Leisegang, Ralph R. Weichselbaum, Wolfgang Uckert, Hua Yu, Thomas Blankenstein, Andreas Herrmann, Dana Briesemeister |
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| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Stromal cell Intravital Microscopy Angiogenesis Vascular Remodeling Article Substrate Specificity Interferon-gamma Mice Necrosis 03 medical and health sciences Ischemia Interferon Cell Line Tumor Neoplasms Animals Medicine Interferon gamma Receptors Interferon Wound Healing Multidisciplinary business.industry Endothelial Cells Cell Hypoxia Haematopoiesis 030104 developmental biology medicine.anatomical_structure Cancer cell Immunology Cancer research Blood Vessels Female Stromal Cells Wound healing business medicine.drug Blood vessel |
| Zdroj: | Nature. 545:98-102 |
| ISSN: | 1476-4687 0028-0836 |
| Popis: | The relative contribution of the effector molecules produced by T cells to tumour rejection is unclear, but interferon-γ (IFNγ) is critical in most of the analysed models1. Although IFNγ can impede tumour growth by acting directly on cancer cells2,3, it must also act on the tumour stroma for effective rejection of large, established tumours4,5. However, which stroma cells respond to IFNγ and by which mechanism IFNγ contributes to tumour rejection through stromal targeting have remained unknown. Here we use a model of IFNγ induction and an IFNγ–GFP fusion protein in large, vascularized tumours growing in mice that express the IFNγ receptor exclusively in defined cell types. Responsiveness to IFNγ by myeloid cells and other haematopoietic cells, including T cells or fibroblasts, was not sufficient for IFNγ-induced tumour regression, whereas responsiveness of endothelial cells to IFNγ was necessary and sufficient. Intravital microscopy revealed IFNγ-induced regression of the tumour vasculature, resulting in arrest of blood flow and subsequent collapse of tumours, similar to non-haemorrhagic necrosis in ischaemia and unlike haemorrhagic necrosis induced by tumour necrosis factor. The early events of IFNγ-induced tumour ischaemia resemble non-apoptotic blood vessel regression during development, wound healing or IFNγ-mediated, pregnancy-induced remodelling of uterine arteries6–8. A better mechanistic understanding of how solid tumours are rejected may aid the design of more effective protocols for adoptive T-cell therapy. |
| Databáze: | OpenAIRE |
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