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

Emily J Colbeck, James P Hindley, Kathryn Smart, Emma Jones, Anja Bloom, Hayley Bridgeman, Rhoanne C McPherson, Darryl G Turner, Kristin Ladell, David A Price, Richard A O'Connor, Stephen M Anderton, Andrew J Godkin, Awen M Gallimore

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)24649-59
Number of pages11
JournalOncotarget
Volume6
Issue number28
DOIs
Publication statusPublished - 22 Sep 2015

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