Characterization of T lymphocytes infiltrating sites of tumor progression and regression during concomitant tumor immunity

Persistent Link:
http://hdl.handle.net/10150/282126
Title:
Characterization of T lymphocytes infiltrating sites of tumor progression and regression during concomitant tumor immunity
Author:
Kurt, Robert Anthony, 1968-
Issue Date:
1996
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 cellular infiltration of solid tumors is indicative of an immune response to cancerous growths. Unfortunately, most tumors grow progressively despite this infiltration. Therefore, the infiltrate from a regressing tumor is necessary in order to examine the requirements for tumor rejection. Due to the rarity of tumor rejection, elucidating the requirements is difficult without an animal model. The sponge model of concomitant tumor immunity allowed the examination of the components associated with tumor rejection. In the model of concomitant tumor immunity an animal is given a primary tumor followed by a secondary tumor challenge. Despite the progression of the primary tumor, the secondary tumor challenge is rejected. In this model the secondary tumor challenge is delivered into a preimplanted gelatin sponge matrix which can be retrieved in order to capture the components associated with tumor rejection. Retrieval of both the primary progressing tumor and the gelatin sponge allowed a direct comparison of the factors associated with tumor progression and rejection. Using this model, we have examined the progressing and rejected tumor sites for differences in T cell cytotoxicity, V beta T cell receptor usage, and the expression of cytokine genes and signal transducing proteins. The results from this study demonstrated that the T cells isolated from progressing tumor sites were not cytolytic, whereas the T cells from the rejection sites showed significant cytolysis towards the autologous tumor cells in vitro. Surprisingly, the T cell infiltration into the progressing and rejected tumor sites were similar with V beta 1 and V beta 8 T cell receptor bearing T cells predominating at both locations. The T cell response also showed clonal restriction upon examination of the complementarity determining region 3 (CDR3) of the T cell receptor. Significantly, the rejection site showed higher gene expression levels of IFN-γ, TNF-α, IL-2, IL-4, IL-10, and IL-12 and reduced TGF-β gene expression compared to the progressing tumor site. Finally, although the T cells from the progressing tumor site showed an altered pattern of tyrosine phosphorylation, the signaling molecules p59ᶠʸⁿ and CD3 ζ were expressed at comparable levels in the T cells from both sites. These data strongly suggest that the tumor microenvironment may play a major role in orchestrating an anti-tumor immune response.
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.titleCharacterization of T lymphocytes infiltrating sites of tumor progression and regression during concomitant tumor immunityen_US
dc.creatorKurt, Robert Anthony, 1968-en_US
dc.contributor.authorKurt, Robert Anthony, 1968-en_US
dc.date.issued1996en_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 cellular infiltration of solid tumors is indicative of an immune response to cancerous growths. Unfortunately, most tumors grow progressively despite this infiltration. Therefore, the infiltrate from a regressing tumor is necessary in order to examine the requirements for tumor rejection. Due to the rarity of tumor rejection, elucidating the requirements is difficult without an animal model. The sponge model of concomitant tumor immunity allowed the examination of the components associated with tumor rejection. In the model of concomitant tumor immunity an animal is given a primary tumor followed by a secondary tumor challenge. Despite the progression of the primary tumor, the secondary tumor challenge is rejected. In this model the secondary tumor challenge is delivered into a preimplanted gelatin sponge matrix which can be retrieved in order to capture the components associated with tumor rejection. Retrieval of both the primary progressing tumor and the gelatin sponge allowed a direct comparison of the factors associated with tumor progression and rejection. Using this model, we have examined the progressing and rejected tumor sites for differences in T cell cytotoxicity, V beta T cell receptor usage, and the expression of cytokine genes and signal transducing proteins. The results from this study demonstrated that the T cells isolated from progressing tumor sites were not cytolytic, whereas the T cells from the rejection sites showed significant cytolysis towards the autologous tumor cells in vitro. Surprisingly, the T cell infiltration into the progressing and rejected tumor sites were similar with V beta 1 and V beta 8 T cell receptor bearing T cells predominating at both locations. The T cell response also showed clonal restriction upon examination of the complementarity determining region 3 (CDR3) of the T cell receptor. Significantly, the rejection site showed higher gene expression levels of IFN-γ, TNF-α, IL-2, IL-4, IL-10, and IL-12 and reduced TGF-β gene expression compared to the progressing tumor site. Finally, although the T cells from the progressing tumor site showed an altered pattern of tyrosine phosphorylation, the signaling molecules p59ᶠʸⁿ and CD3 ζ were expressed at comparable levels in the T cells from both sites. These data strongly suggest that the tumor microenvironment may play a major role in orchestrating an anti-tumor immune response.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.proquest9706169en_US
dc.identifier.bibrecord.b34290229en_US
All Items in UA Campus Repository are protected by copyright, with all rights reserved, unless otherwise indicated.