Immune Cell Subsets Direct or Antagonize Tumor Immunity: Promotion of TH1 Responses in Tumor Vaccination

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dc.contributor.authorPressley, Jennifer Sparkmanen
dc.contributor.committeechairElgert, Klaus D.en
dc.contributor.committeememberGogal, Robert M. Jr.en
dc.contributor.committeememberBurger, Carol J.en
dc.contributor.committeememberBassaganya-Riera, Josepen
dc.contributor.departmentBiologyen
dc.date.accessioned2014-03-14T20:39:46Zen
dc.date.adate2005-07-07en
dc.date.available2014-03-14T20:39:46Zen
dc.date.issued2005-06-02en
dc.date.rdate2006-07-07en
dc.date.sdate2005-06-10en
dc.description.abstractTumors evade immune system tumor-controlling functions. T cells critical to antitumor immunity are tolerogenic in tumor-burdened animals, and fail to lyse neoplastic cells. Our goal was to investigate the kinetics of immune dysfunction related to tumor-burdened host (TBH) memory T cell responses (or the lack thereof). We demonstrate tumor growth impairs T cell activation by modulating CD4+ T cell infiltration and systemic CD44 and CD62L activation marker expression, and by downregulating TBH TH1 cytokine production by splenic CD4+ T cells. Since chemotherapeutic treatments have potent cytostatic effects, we posited they enhance T cell dysfunctionality; which leads to limited therapeutic efficacy. Paclitaxel is a potent chemotherapeutic agent currently being administered in Stage III clinical trials; however, it reduces T cell proliferative capacity and interferon-γ (IFN-γ) production. In contrast, our data suggest that administration of low dose paclitaxel prolongs adaptive immunity in a limited capacity. We show paclitaxel enhances CD4highCD62Llow cell populations that drive TH1 cytokine production and prolongs the production of interleukin-2 (IL-2) in TBHs. We hypothesize that the initiation and maintenance of activated TH1 cell populations in patients during therapy serves as a reliable prognostic indicator of a favorable therapeutic response. Paclitaxel's limited therapeutic effects are due, in part, to its suppression of T cell activities; but the administration of low dose chemotherapy in combination with immunotherapeutic agents temporally takes advantage of paclitaxel's immunostimulatory capabilities. Our work will enhance current understanding of immune dysregulation during cancer development, and promote advances in the monitoring and development of combinatorial cancer treatments.en
dc.description.degreeMaster of Scienceen
dc.identifier.otheretd-06102005-132007en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-06102005-132007/en
dc.identifier.urihttp://hdl.handle.net/10919/33509en
dc.publisherVirginia Techen
dc.relation.haspartMSThesisFinal.pdfen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectcytokinesen
dc.subjectpaclitaxelen
dc.subjectCD4+ T cellsen
dc.subjectimmunotherapyen
dc.subjecttumorsen
dc.subjectmacrophagesen
dc.titleImmune Cell Subsets Direct or Antagonize Tumor Immunity: Promotion of TH1 Responses in Tumor Vaccinationen
dc.typeThesisen
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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