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Ex-Th17 Foxp3+ T cells - a novel subset of Foxp3+ T cells induced in cancer
  1. Stephanie Downs-Canner1,
  2. Roshni Ravindranathan1,
  3. Robert P Edwards2,
  4. Pawel Kalinski1,
  5. Kunle Odunsi3,
  6. David L Bartlett1 and
  7. Natasa Obermajer1
  1. Aff1 grid.21925.3d0000000419369000University of Pittsburgh Pittsburgh PA USA
  2. Aff2 grid.460217.60000000403874432Magee-Womens Research Institute Ovarian Cancer Center of Excellence Pittsburgh PA USA
  3. Aff3 grid.240614.50000000121818635Roswell Park Cancer Institute Buffalo NY USA

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Meeting abstracts

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.