title: Interleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells.
abstract: IL-21 is known to promote anti-tumour immunity due to its ability to promote T cell responses and counteract Treg-mediated suppression. It has also been shown to limit Treg frequencies during tumour-antigen stimulations. However, whether this represents inhibition of FOXP3 induction in naïve CD4 T cells or curtailed expansion of natural Treg remains unclear. Moreover, whether this effect is maintained in an environment of tumour-derived immunosuppressive factors is not known. Here, we show that in the context of a number of cancers, naïve CD45RA+ CD4 T cells are induced to express high levels of FOXP3, and that FOXP3 expression correlates with inhibition of T cell proliferation. FOXP3 expression was most potently induced by tumours secreting higher levels of total and active TGFβ1 and this induction could be potently counteracted with IL-21, restoring T cell proliferation. We conclude that Treg induction in naïve T cells is a common phenomenon amongst a number of different cancers and that the ability of IL-21 to counteract this effect is further evidence of its promise in cancer therapy.
authors.affiliation: Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK.
authors.forename: Vinodh
authors.initials: V
authors.lastname: Kannappan
authors.affiliation: Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK.
authors.forename: Kate
authors.initials: K
authors.lastname: Butcher
authors.affiliation: Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Trela
authors.affiliation: Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK.
authors.forename: Iain
authors.initials: I
authors.lastname: Nicholl
authors.affiliation: Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK.
authors.forename: Weiguang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Research Institute in Healthcare Science, University of Wolverhampton, Wolverhampton, UK. k.attridge@aston.ac.uk.|School of Life and Health Sciences, MB Building, Aston University, Aston Triangle, B4 7ET, Birmingham, UK. k.attridge@aston.ac.uk.
authors.forename: Kesley
authors.identifier: http://orcid.org/0000-0003-4521-9009
authors.initials: K
authors.lastname: Attridge
mesh_terms: D000072283:A549 Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000276:immunology*; D045325:HCT116 Cells; D006801:Humans; D007378:Interleukins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007378:Interleukins; D000098546:Interleukin-21
keywords: Anti-tumour immunity; FOXP3; IL-21; Immunosuppression; Immunotherapy; Regulatory T cells