Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 66, Issue 5, Pages 637-645Publisher
SPRINGER
DOI: 10.1007/s00262-017-1970-6
Keywords
Regulatory T cells; FOXP3; Immunosuppression; IL-21; Immunotherapy; Anti-tumour immunity
Categories
Funding
- institutional early researcher award
- Cancer and Polio Research Fund
- BD Biosciences
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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 naive 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, naive 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 TGF beta 1 and this induction could be potently counteracted with IL-21, restoring T cell proliferation. We conclude that Treg induction in naive 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.
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