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Ex-Th17 Foxp3+ T cells - a novel subset of Foxp3+ T cells induced in cancer

  • Stephanie Downs-Canner1,
  • Roshni Ravindranathan1,
  • Robert P Edwards2,
  • Pawel Kalinski1,
  • Kunle Odunsi3,
  • David L Bartlett1 and
  • Natasa Obermajer1
Journal for ImmunoTherapy of Cancer20153(Suppl 2):P273

https://doi.org/10.1186/2051-1426-3-S2-P273

Published: 4 November 2015

Keywords

Ovarian CancerTh17 CellTreg CellHuman Ovarian CancerFoxp3 Expression

Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17-Treg misbalance associates with inflammation.

We demonstrate that in addition to natural (n)Treg and induced (i)Treg cells developed from naïve precursors, Th17 cells are a novel source of Foxp3+ cells by converting into ex-Th17 Foxp3+ cells, and this helps to reconcile the contradictory information about the relevance in particularly of Th17 subset in immune surveillance.

We identified IL-17A+Foxp3+ double-positive and ex-IL-17-producing IL-17A-Foxp3+ T cells to be the underlying mechanism of immune regulation in mesenchymal stem cell-mediated prolonged allograft survival. Further, we identified accumulation of IL17A+Foxp3+ and ex-Th17 Foxp3+ cells in tumor bearing mice, indicating progressive direct Th17-into-Treg cell conversion as a novel phenomenon in cancer.

Moreover, we determined the importance of the Th17 cell plasticity for tumor induction and/or progression in ROR-g-/- mice. Our data indicate that RORgt is required not only for Th17 development, but also for effective Treg cell induction. TGF-b1 induced Foxp3 expression was reduced in ROR-g -/- cells. Further, tumor bearing ROR-g-/- mice showed significantly less Foxp3+ Treg cells, but higher IFNg+ Tcells compared to wild type animals.

Increased infiltration of IL17+ and FoxP3+ CD4+ T cells in the human ovarian cancer ascites, with the presence of a distinct IL17+FoxP3+ subset, and a significant correlation between tumor-associated Th17 and Treg cells demonstrates the existence of Th17-Foxp3+ T cell inter-relationship in cancer patients.

Yin-yang of IL17+ and Foxp3+ is important principle for improved clinical approaches targeting responses against self, allo and/or neo-self.

Authors’ Affiliations

(1)
University of Pittsburgh, Pittsburgh, USA
(2)
Magee-Womens Research Institute Ovarian Cancer Center of Excellence, Pittsburgh, USA
(3)
Roswell Park Cancer Institute, Buffalo, USA

Copyright

© Downs-Canner et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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