Interleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells

Vinodh Kannappan, Kate Butcher, Malgorzata Trela, Iain Nicholl, Weiguang Wang, Kesley Attridge*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)637–645
JournalCancer immunology, immunotherapy : CII
Issue number5
Early online date27 Feb 2017
Publication statusPublished - 1 May 2017

Bibliographical note

© The Author(s) 2017. This article is published with open access at


  • regulatory T cells
  • FOXP
  • immunosuppression
  • IL-21
  • immunotherapy
  • antitumour immunity


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