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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 1/2013

01-01-2013 | Original article

Generation and immunologic functions of Th17 cells in malignant gliomas

Authors: Manjeera Paladugu, Archana Thakur, Lawrence G. Lum, Sandeep Mittal, Prahlad Parajuli

Published in: Cancer Immunology, Immunotherapy | Issue 1/2013

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Abstract

Th17 cells, a recently discovered inflammatory T cell subtype, have been implicated with autoimmune disorders. However, mechanism of generation or functions of intratumoral Th17 cells are still unclear. We have been investigating the mechanism of induction and role of Th17 cells in malignant gliomas using primary tumor as well as cell lines. We report here that: (1) a higher frequency of Th17 cells in gliomas were associated with higher number of myeloid (CD11b) cells as well as the expression of TGF-β1 or IL-6; (2) conditioned medium from glioma cells (Gl CM) induced Th17 cell differentiation, which was inhibited by anti-TGF-β1 and anti-IL-6; (3) glioma-associated monocytes secreted Th17-promoting cytokines IL-1β and IL-23; (4) CM from glioma and monocyte co-culture (Gl+Mo CM) induced high frequency of Th17 cells in naïve T cell culture, which was abrogated by anti-IL-1β and anti-IL-23 antibodies; (5) In vitro Gl+Mo CM-mediated Th17 generation was associated with a decrease in IFN-γ and a concomitant increase in IL-10 secretion. Anti-TGF-β1, but not anti-IL-6, significantly reversed this cytokine profile. These results demonstrate prevalence of Th17 cells in gliomas and implicate the cytokines derived from the tumor as well as infiltrating myeloid cells in the induction of Th17 cells in glioma microenvironment. Moreover, the data also suggest that glioma-associated Th17 cells may contribute to immune-suppression via TGF-β1-induced IL-10 secretion. Further studies on the mechanism of tumor-infiltration, developmental pathways, and pro-/anti-tumor functions of Th17 cells will provide rationale for developing novel adjuvant immunotherapeutic strategies for malignant gliomas.
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Metadata
Title
Generation and immunologic functions of Th17 cells in malignant gliomas
Authors
Manjeera Paladugu
Archana Thakur
Lawrence G. Lum
Sandeep Mittal
Prahlad Parajuli
Publication date
01-01-2013
Publisher
Springer-Verlag
Published in
Cancer Immunology, Immunotherapy / Issue 1/2013
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-012-1312-7

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