Priority Research Papers: Immunology:

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 and Awen M. Gallimore _

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Oncotarget. 2015; 6:24649-24659. https://doi.org/10.18632/oncotarget.5584

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Emily J. Colbeck1,*, James P. Hindley1,*, Kathryn Smart1, Emma Jones1, Anja Bloom1, Hayley Bridgeman1, Rhoanne C. McPherson2, Darryl G. Turner2, Kristin Ladell1, David A. Price1, Richard A. O’Connor2, Stephen M. Anderton2, Andrew J. Godkin1 and Awen M. Gallimore1

1 Institute of Infection Immunity and Biochemistry, Cardiff University School of Medicine, Cardiff, UK

2 MRC Centre for Inflammation Research, Centre for Multiple Sclerosis Research and Centre for Immunity Infection and Evolution, University of Edinburgh, Edinburgh, UK

* These authors have Contributed equally to this work

Correspondence to:

Awen M. Gallimore, email:

Keywords: Treg, cancer, proliferation, T-bet, CD69, Immunology Section, Immunity, Immune response

Received: July 18, 2015 Accepted: August 22, 2015 Published: September 10, 2015


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.

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