Eliminating roles for T-bet and IL-2 but revealing superior activation and proliferation as mechanisms underpinning dominance of regulatory T cells in tumors

Colbeck, Emily, Hindley, James P., Smart, Kathryn, Jones, Emma, Bloom, Anja, Bridgeman, Hayley, McPherson, Rhoanne C., Turner, Darryl G., Ladell, Kristin Ingrid, Price, David, O'Connor, Richard A., Anderton, Stephen M., Godkin, Andrew James and Gallimore, Awen Myfanwy 2015. Eliminating roles for T-bet and IL-2 but revealing superior activation and proliferation as mechanisms underpinning dominance of regulatory T cells in tumors. Oncotarget 6 (28) , pp. 24649-24659. 10.18632/oncotarget.5584

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Abstract

Foxp3+ regulatory T cells (Tregs) are often highly enriched within the tumorinfiltrating T cell pool. Using a well-characterised model of carcinogen-induced fibrosarcomas we show that the enriched tumor-infiltrating Treg population comprises largely of CXCR3+ T-bet+ ‘TH1-like’ Tregs which are thymus-derived Helios+ cells. Whilst IL-2 maintains homeostatic ratios of Tregs in lymphoid organs, we found that the perturbation in Treg frequencies in tumors is IL-2 independent. Moreover, we show that the TH1 phenotype of tumor-infiltrating Tregs is dispensable for their ability to influence tumor progression. We did however find that unlike Tconvs, the majority of intra-tumoral Tregs express the activation markers CD69, CD25, ICOS, CD103 and CTLA4 and are significantly more proliferative than Tconvs. Moreover, we have found that CD69+ Tregs are more suppressive than their CD69- counterparts. Collectively, these data indicate superior activation of Tregs in the tumor microenvironment, promoting their suppressive ability and selective proliferation at this site.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Impact Journals LLC
ISSN:	1949-2553
Funders:	Wellcome
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	22 August 2015
Last Modified:	21 Jan 2019 23:09
URI:	http://orca.cf.ac.uk/id/eprint/78074

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