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IL-17A mediated endothelial breach promotes metastasis formation


Kulig, Paulina; Burkhard, Sara; Mikita-Geoffroy, Joanna; Croxford, Andrew L; Hövelmeyer, Nadine; Gyülveszi, Gabor; Gorzelanny, Christian; Waisman, Ari; Borsig, Lubor; Becher, Burkhard (2016). IL-17A mediated endothelial breach promotes metastasis formation. Cancer immunology research, 4(1):26-32.

Abstract

The role of the IL-23/IL-17A axis in tumor-immune interactions is a matter of controversy. While some suggest that IL-17A producing T cells (TH17) can suppress tumor growth, others report that IL-17A and IL-23 accelerate tumor growth. Here, we systematically assessed the impact of IL-17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate-mapping revealed that IL-17A was secreted within lung metastases predominantly by γδ T cells, while TH17 cells were virtually absent. Using different tumor models, we found Il17a-/- mice to consistently develop fewer pulmonary tumor colonies. IL-17A specifically increased blood vessel permeability and the expression of E-selectin and VCAM-1 by lung endothelial cells in vivo. In transgenic mice, specific targeting of IL-17A to the endothelium increased the number of tumor foci. Moreover, the direct impact of IL-17A on lung endothelial cells resulted in impaired endothelial barrier integrity showing that IL-17A promotes the formation of lung metastases through tumor-endothelial transmigration.

Abstract

The role of the IL-23/IL-17A axis in tumor-immune interactions is a matter of controversy. While some suggest that IL-17A producing T cells (TH17) can suppress tumor growth, others report that IL-17A and IL-23 accelerate tumor growth. Here, we systematically assessed the impact of IL-17A-secreting lymphocytes in several murine models of tumor lung metastasis. Genetic fate-mapping revealed that IL-17A was secreted within lung metastases predominantly by γδ T cells, while TH17 cells were virtually absent. Using different tumor models, we found Il17a-/- mice to consistently develop fewer pulmonary tumor colonies. IL-17A specifically increased blood vessel permeability and the expression of E-selectin and VCAM-1 by lung endothelial cells in vivo. In transgenic mice, specific targeting of IL-17A to the endothelium increased the number of tumor foci. Moreover, the direct impact of IL-17A on lung endothelial cells resulted in impaired endothelial barrier integrity showing that IL-17A promotes the formation of lung metastases through tumor-endothelial transmigration.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:January 2016
Deposited On:11 Dec 2015 14:13
Last Modified:05 Apr 2016 19:36
ISSN:2326-6074
Publisher DOI:https://doi.org/10.1158/2326-6066.CIR-15-0154
PubMed ID:26586773

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