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

Kannappan, Vinodh, Butcher, Kate, Trela, Malgorzata, Nicholl, Iain, Wang, Weiguang and Attridge, Kesley (2017). Interleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells. Cancer immunology, immunotherapy : CII, In pre ,

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.

Publication DOI: https://doi.org/10.1007/s00262-017-1970-6
Divisions: Life & Health Sciences
Additional Information: © The Author(s) 2017. This article is published with open access at Springerlink.com
Uncontrolled Keywords: regulatory T cells,FOXP,immunosuppression,IL-21,immunotherapy,antitumour immunity,Immunology and Allergy,Immunology,Oncology,Cancer Research
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2017-02-27
Published Online Date: 2017-02-27
Authors: Kannappan, Vinodh
Butcher, Kate
Trela, Malgorzata
Nicholl, Iain
Wang, Weiguang
Attridge, Kesley ( 0000-0003-4521-9009)

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