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

2.50
Hdl Handle:
http://hdl.handle.net/2436/620406
Title:
Interleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells
Authors:
Kannappan, Vinodh; Butcher, Kate; Trela, Malgorzata; Nicholl, Iain ( 0000-0003-3803-7039 ) ; Wang, Weiguang; Attridge, Kesley ( 0000-0003-4521-9009 )
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.
Citation:
Interleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells 2017 Cancer Immunology, Immunotherapy
Publisher:
Springer
Journal:
Cancer Immunology, Immunotherapy
Issue Date:
27-Feb-2017
URI:
http://hdl.handle.net/2436/620406
DOI:
10.1007/s00262-017-1970-6
Additional Links:
http://link.springer.com/10.1007/s00262-017-1970-6
Type:
Article
Language:
en
ISSN:
0340-7004
Appears in Collections:
FSE

Full metadata record

DC FieldValue Language
dc.contributor.authorKannappan, Vinodhen
dc.contributor.authorButcher, Kateen
dc.contributor.authorTrela, Malgorzataen
dc.contributor.authorNicholl, Iainen
dc.contributor.authorWang, Weiguangen
dc.contributor.authorAttridge, Kesleyen
dc.date.accessioned2017-03-08T16:40:43Z-
dc.date.available2017-03-08T16:40:43Z-
dc.date.issued2017-02-27-
dc.identifier.citationInterleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cells 2017 Cancer Immunology, Immunotherapyen
dc.identifier.issn0340-7004en
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.en
dc.language.isoenen
dc.publisherSpringeren
dc.relation.urlhttp://link.springer.com/10.1007/s00262-017-1970-6en
dc.rightsArchived with thanks to Cancer Immunology, Immunotherapyen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectRegulatory T cellsen
dc.subjectFOXP3en
dc.subjectImmunosuppressionen
dc.subjectIL-21en
dc.subjectImmunotherapyen
dc.subjectAnti-tumour immunityen
dc.titleInterleukin 21 inhibits cancer-mediated FOXP3 induction in naïve human CD4 T cellsen
dc.typeArticleen
dc.identifier.journalCancer Immunology, Immunotherapyen
dc.date.accepted2017-02-
rioxxterms.funderThis work was funded by an institutional early researcher award and by research grants from the Cancer and Polio Research Fund and BD Biosciences, all to Kesley Attridgeen
rioxxterms.identifier.projectUoW080317IDNen
rioxxterms.versionVoRen
rioxxterms.licenseref.urihttps://creativecommons.org/CC BY-NC-ND 4.0en
rioxxterms.licenseref.startdate2017-03-08en
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