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dc.contributor.authorKannappan, Vinodh
dc.contributor.authorButcher, Kate
dc.contributor.authorTrela, Malgorzata
dc.contributor.authorNicholl, Iain
dc.contributor.authorWang, Weiguang
dc.contributor.authorAttridge, Kesley
dc.date.accessioned2017-03-08T16:40:43Z
dc.date.available2017-03-08T16:40:43Z
dc.date.issued2017-02-27
dc.identifier.citationKannappan, V., Butcher, K., Trela, M., Nicholl, I., Wang, W and Attridge, K. (2017) 'Interleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells', Cancer Immunology, Immunotherapy, 66 (5) pp. 637-645. doi: 10.1007/s00262-017-1970-6
dc.identifier.issn0340-7004
dc.identifier.doi10.1007/s00262-017-1970-6
dc.identifier.urihttp://hdl.handle.net/2436/620406
dc.description.abstractIL-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.
dc.language.isoen
dc.publisherSpringer
dc.relation.urlhttp://link.springer.com/10.1007/s00262-017-1970-6
dc.subjectRegulatory T cells
dc.subjectFOXP3
dc.subjectImmunosuppression
dc.subjectIL-21
dc.subjectImmunotherapy
dc.subjectAnti-tumour immunity
dc.titleInterleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells
dc.typeJournal article
dc.identifier.journalCancer Immunology, Immunotherapy
dc.date.accepted2017-02-03
rioxxterms.funderUniversity of Wolverhampton
rioxxterms.identifier.projectUoW080317IDN
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0
rioxxterms.licenseref.startdate2017-03-08
dc.source.volume66
dc.source.issue5
dc.source.beginpage637
dc.source.endpage645
refterms.dateFCD2018-10-19T09:26:31Z
refterms.versionFCDVoR
refterms.dateFOA2017-03-08T00:00:00Z
html.description.abstractIL-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.


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