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 ORCID: https://orcid.org/0000-0002-9856-2938, Price, David ORCID: https://orcid.org/0000-0001-9416-2737, O'Connor, Richard A., Anderton, Stephen M., Godkin, Andrew James ORCID: https://orcid.org/0000-0002-1910-7567 and Gallimore, Awen Myfanwy ORCID: https://orcid.org/0000-0001-6675-7004 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 tumor-infiltrating 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
ISSN:	1949-2553
Funders:	Wellcome
Date of First Compliant Deposit:	30 March 2016
Date of Acceptance:	22 August 2015
Last Modified:	02 May 2023 17:42
URI:	https://orca.cardiff.ac.uk/id/eprint/78074

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