NEGATIVE REGULATION OF REGULATORY T CELLS BY MYELOID-DERIVED SUPPRESSOR CELLS IN CANCER

Persistent Link:
http://hdl.handle.net/10150/145099
Title:
NEGATIVE REGULATION OF REGULATORY T CELLS BY MYELOID-DERIVED SUPPRESSOR CELLS IN CANCER
Author:
Centuori, Sara Mozelle
Issue Date:
2011
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
Abstract:
Myeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) play an essential role in the immunosuppressive networks that contribute to tumor immune evasion. The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-regulation between MDSC and Treg remain incompletely defined. The current work evaluates the influence of MDSC, expanded in two mouse cancer models, on immunosuppressive Treg. We demonstrate that tumor-induced MDSC endowed with the potential of suppressing conventional T lymphocytes surprisingly impair TGF-β1-mediated generation of induced Treg (iTreg) from naïve CD4⁺ T lymphocytes. Suppression of iTreg generation by MDSC occurs early in the differentiation process, and is cell contact dependent. This inhibition of FoxP3-expressing T lymphocyte differentiation by MDSC does not depend on arginase 1, cystine/cysteine depletion, iNOS/NO, or PD-1/PD-L1 signaling. These findings therefore indicate that MDSC from tumor-bearing hosts have the heretofore unreported ability to restrict some immunosuppressive Treg subpopulations.
Type:
Electronic Dissertation; text
Keywords:
Cancer; immunosuppressive cells; MDSC; Myeloid-derived suppressor cells; Regulatory T cells; Treg
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Cancer Biology
Degree Grantor:
University of Arizona
Advisor:
Katsanis, Emmanuel; Larmonier, Nicolas

Full metadata record

DC FieldValue Language
dc.language.isoenen_US
dc.titleNEGATIVE REGULATION OF REGULATORY T CELLS BY MYELOID-DERIVED SUPPRESSOR CELLS IN CANCERen_US
dc.creatorCentuori, Sara Mozelleen_US
dc.contributor.authorCentuori, Sara Mozelleen_US
dc.date.issued2011-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.en_US
dc.description.abstractMyeloid-derived suppressor cells (MDSC) and regulatory T cells (Treg) play an essential role in the immunosuppressive networks that contribute to tumor immune evasion. The mechanisms by which tumors promote the expansion and/or function of these suppressive cells and the cross-regulation between MDSC and Treg remain incompletely defined. The current work evaluates the influence of MDSC, expanded in two mouse cancer models, on immunosuppressive Treg. We demonstrate that tumor-induced MDSC endowed with the potential of suppressing conventional T lymphocytes surprisingly impair TGF-β1-mediated generation of induced Treg (iTreg) from naïve CD4⁺ T lymphocytes. Suppression of iTreg generation by MDSC occurs early in the differentiation process, and is cell contact dependent. This inhibition of FoxP3-expressing T lymphocyte differentiation by MDSC does not depend on arginase 1, cystine/cysteine depletion, iNOS/NO, or PD-1/PD-L1 signaling. These findings therefore indicate that MDSC from tumor-bearing hosts have the heretofore unreported ability to restrict some immunosuppressive Treg subpopulations.en_US
dc.typeElectronic Dissertationen_US
dc.typetexten_US
dc.subjectCanceren_US
dc.subjectimmunosuppressive cellsen_US
dc.subjectMDSCen_US
dc.subjectMyeloid-derived suppressor cellsen_US
dc.subjectRegulatory T cellsen_US
dc.subjectTregen_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineCancer Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorKatsanis, Emmanuelen_US
dc.contributor.advisorLarmonier, Nicolasen_US
dc.contributor.committeememberLybarger, Lonnieen_US
dc.contributor.committeememberDoetschman, Tomen_US
dc.contributor.committeememberBriehl, Margareten_US
dc.contributor.committeememberBowden, Timen_US
dc.identifier.proquest11517-
dc.identifier.oclc752261380-
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