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01-12-2011 | Original article

A critical role for regulatory T cells in driving cytokine profiles of Th17 cells and their modulation of glioma microenvironment

Authors: Gabriele Cantini, Federica Pisati, Alfonso Mastropietro, Véronique Frattini, Yoichiro Iwakura, Gaetano Finocchiaro, Serena Pellegatta

Published in: Cancer Immunology, Immunotherapy | Issue 12/2011

Abstract

IL-17A, produced by Th17 cells, may play a dual role in antitumor immunity. Using the GL261-glioma model, we investigated the effects of Th17 cells on tumor growth and microenvironment. Th17 cells infiltrate mouse gliomas, increase significantly in a time-dependent manner similarly to Treg and do not express Foxp3. To characterize the direct effects of Th17 cells on GL261 murine gliomas and on tumor microenvironment, we isolated IL-17-producing cells enriched from splenocytes derived from naïve (nTh17) or glioma-bearing mice (gTh17) and pre-stimulated in vitro with or without TGF-β. Spleen-derived Th17 cells co-expressing IL-17, IFN-γ and IL-10, but not Treg marker Foxp3, were co-injected intracranially with GL261 in immune-competent mice. Mice co-injected with GL261 and nTh17 survived significantly longer than gTh17 (P < 0.006) and gliomas expressed high level of IFN-γ and TNF-α, low levels of IL-10 and TGF-β. In vitro IL-17 per se did not exert effects on GL261 proliferation; in vivo gliomas grew equally well intracranially in IL-17 deficient and wild-type mice. We further analyzed relationship between Th17 cells and Treg. Treg were significantly higher in splenocytes from glioma-bearing than naïve mice (P = 0.01) and gTh17 produced more IL-10 than IFN-γ (P = 0.002). In vitro depletion of Treg using PC61 in splenocytes from glioma-bearing mice causes increased IL-17/IFN-γ cells (P = 0.007) and decreased IL-17/IL-10 cells (P = 0.03). These results suggest that Th17 polarization may be induced by Treg and that Th17 cells in gliomas modulate tumor growth depending on locally produced cytokines.

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Title: A critical role for regulatory T cells in driving cytokine profiles of Th17 cells and their modulation of glioma microenvironment
Authors: Gabriele Cantini
Federica Pisati
Alfonso Mastropietro
Véronique Frattini
Yoichiro Iwakura
Gaetano Finocchiaro
Serena Pellegatta
Publication date: 01-12-2011
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 12/2011
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-011-1069-4

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