Dataset Information

Suppressive IL-17A⁺Foxp3⁺ and ex-Th17 IL-17A^negFoxp3⁺ T_reg cells are a source of tumour-associated T_reg cells.

ABSTRACT: Th17 and regulatory T (T_reg) cells are integral in maintaining immune homeostasis and Th17-T_reg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3⁺ cells. In addition to natural (n)T_reg and induced (i)T_reg cells that develop from naive precursors, suppressive IL-17A⁺Foxp3⁺ and ex-Th17 Foxp3⁺ cells are converted from IL-17A⁺Foxp3^neg cells in tumour-bearing mice. Metabolic phenotyping of Foxp3-expressing IL-17A⁺, ex-Th17 and iT_reg cells demonstrates the dissociation between the metabolic fitness and the suppressive function of Foxp3-expressing T_reg cell subsets. Although all Foxp3-expressing subsets are immunosuppressive, glycolysis is a prominent metabolic pathway exerted only by IL-17A⁺Foxp3⁺ cells. Transcriptome analysis and flow cytometry of IL-17A⁺Foxp3⁺ cells indicate that Folr4, GARP, Itgb8, Pglyrp1, Il1rl1, Itgae, TIGIT and ICOS are Th17-to-T_reg cell transdifferentiation-associated markers. Tumour-associated Th17-to-T_reg cell conversion identified here provides insights for targeting the dynamism of Th17-T_reg cells in cancer immunotherapy.

SUBMITTER: Downs-Canner S

PROVIDER: S-EPMC5355894 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Suppressive IL-17A+Foxp3+ and ex-Th17 IL-17AnegFoxp3+ Treg cells are a source of tumour-associated Treg cells.

Downs-Canner Stephanie S Berkey Sara S Delgoffe Greg M GM Edwards Robert P RP Curiel Tyler T Odunsi Kunle K Bartlett David L DL Obermajer Nataša N

Nature communications 20170314

Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17-Treg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3+ cells. In addition to natural (n)Treg and induced (i)Treg cells that develop from naive precursors, suppressive IL-17A+Foxp3+ and ex-Th17 Foxp3+ cells are converted from IL-17A<s ...[more]

PMID: 28290453

Similar Datasets

Project description:ObjectivesTNF-α inhibitors are widely used in rheumatoid arthritis (RA) with varying success. Response to TNF-α inhibition may reflect the evolution of rheumatoid inflammation through fluctuating stages of TNF-α dependence. Our aim was to assess plasma concentrations of Th-17-related cytokines and the presence of circulating effector T-cells to identify predictors of response to TNF-α inhibitors.MethodsNinety-three people with RA were seen prior to and 4-6 months after commencing etanercept or adalimumab. Plasma concentrations of Th17-related cytokines, circulating effector T-cells, their production of relevant transcription factors and intracellular cytokines were measured at baseline. EULAR response criteria were used to define poor (ΔDAS28 ≤ 1.2 and/or DAS28 > 3.2) and good (ΔDAS28 > 1.2 and DAS28 ≤ 3.2) responders. Multivariate logistic regression was used to identify predictors of response.ResultsParticipants with plasma IL-23 present at baseline were more likely to be poor responders [15/20 (75%) of IL-23+ versus 36/73 (49.3%) of IL-23-; p = 0.041]. While frequencies of Th1, Th17, ex-Th17 and Treg cell populations were similar between good and poor responders to anti-TNF therapy, IL-17A+IFNγ+ ex-Th17 cells were more prevalent in good responders (0.83% of ex-TH17 cells) compared to poor responders (0.24% of ex-Th17 cells), p = 0.023. Both plasma IL-23 cytokine status (OR = 0.17 (95% CI 0.04-0.73)) and IL-17A+IFNγ+ ex-Th17 cell frequency (OR = 1.64 (95% CI 1.06 to 2.54)) were independently associated with a good response to anti-TNF therapy. Receiver operator characteristic (ROC) analysis, including both parameters, demonstrated an area under the ROC curve (AUC) of 0.70 (95% CI 0.60-0.82; p = 0.001).ConclusionsPlasma IL-23 and circulating IL-17A+IFNγ+ ex-Th17 cells are independently associated with response to anti-TNF therapy. In combination, plasma IL-23 and circulating IL-17A+IFNγ+ ex-Th17 cells provide additive value to the prediction of response to anti-TNF therapy in RA.

Dataset Information

Suppressive IL-17A⁺Foxp3⁺ and ex-Th17 IL-17A^negFoxp3⁺ T_reg cells are a source of tumour-associated T_reg cells.

Publications

Suppressive IL-17A<sup>+</sup>Foxp3<sup>+</sup> and ex-Th17 IL-17A<sup>neg</sup>Foxp3<sup>+</sup> T<sub>reg</sub> cells are a source of tumour-associated T<sub>reg</sub> cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets