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Tumour ischaemia by interferon-γ resembles physiological blood vessel regression
- Source :
- Nature. 545:98-102
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 14764687 and 00280836
- Volume :
- 545
- Database :
- OpenAIRE
- Journal :
- Nature
- Accession number :
- edsair.doi.dedup.....a2485e0ff3cac82a3ae7eb4fc063bf3d