The effect of transforming growth factor-beta on dendritic cell-based cancer vaccines

Persistent Link:
http://hdl.handle.net/10150/289946
Title:
The effect of transforming growth factor-beta on dendritic cell-based cancer vaccines
Author:
Kobie, James J.
Issue Date:
2003
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:
The ability of dendritic cells (DCs) to stimulate tumor-specific T lymphocyte responses has made them prime candidates for cancer immunotherapy. Numerous studies have focused on enhancing the ability of DCs to stimulate the immune response. Commonly overlooked is the immunosuppressive milieu of the tumor microenvironment. Many tumor types including the murine mammary carcinoma cell line 4T1, produce large quantities of the immunosuppressive cytokine transforming growth factor-beta (TGF-β). These studies have determined that TGF-β suppresses numerous dendritic cell functions involved in generating an effective anti-tumor immune response. By reducing the amount of TGF-β present in the tumor-bearing host the migratory ability and anti-tumor activity of DCs are enhanced. Adenovirus-mediated Smad7 gene transfer, was able to reduce the responsiveness of DCs to TGF-β in vitro. Vaccination of tumor-bearing mice with AdSmad7-infected DCs resulted in enhanced IFN-γ secretion by tumor draining lymph node (TDLN) cells. However, this did not translate to improved ant-tumor activity. These results stress the necessity to eliminate tumor-derived immunosuppressive molecules such as TGF-β in order to improve the effectiveness of DC-based vaccines in treating cancer.
Type:
text; Dissertation-Reproduction (electronic)
Keywords:
Health Sciences, Immunology.; Health Sciences, Oncology.
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Microbiology and Immunology
Degree Grantor:
University of Arizona
Advisor:
Akporiaye, Emmanuel T.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleThe effect of transforming growth factor-beta on dendritic cell-based cancer vaccinesen_US
dc.creatorKobie, James J.en_US
dc.contributor.authorKobie, James J.en_US
dc.date.issued2003en_US
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.abstractThe ability of dendritic cells (DCs) to stimulate tumor-specific T lymphocyte responses has made them prime candidates for cancer immunotherapy. Numerous studies have focused on enhancing the ability of DCs to stimulate the immune response. Commonly overlooked is the immunosuppressive milieu of the tumor microenvironment. Many tumor types including the murine mammary carcinoma cell line 4T1, produce large quantities of the immunosuppressive cytokine transforming growth factor-beta (TGF-β). These studies have determined that TGF-β suppresses numerous dendritic cell functions involved in generating an effective anti-tumor immune response. By reducing the amount of TGF-β present in the tumor-bearing host the migratory ability and anti-tumor activity of DCs are enhanced. Adenovirus-mediated Smad7 gene transfer, was able to reduce the responsiveness of DCs to TGF-β in vitro. Vaccination of tumor-bearing mice with AdSmad7-infected DCs resulted in enhanced IFN-γ secretion by tumor draining lymph node (TDLN) cells. However, this did not translate to improved ant-tumor activity. These results stress the necessity to eliminate tumor-derived immunosuppressive molecules such as TGF-β in order to improve the effectiveness of DC-based vaccines in treating cancer.en_US
dc.typetexten_US
dc.typeDissertation-Reproduction (electronic)en_US
dc.subjectHealth Sciences, Immunology.en_US
dc.subjectHealth Sciences, Oncology.en_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineMicrobiology and Immunologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorAkporiaye, Emmanuel T.en_US
dc.identifier.proquest3107010en_US
dc.identifier.bibrecord.b44663171en_US
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