Regulation of macrophage activities by tumor growth: mechanisms of immunosuppression

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dc.contributor.authorAlleva, David G.en
dc.contributor.committeechairElgert, Klaus D.en
dc.contributor.committeememberAhmed, S. Ansaren
dc.contributor.committeememberLederman, Muriel L.en
dc.contributor.committeememberBurger, Carol J.en
dc.contributor.committeememberSchurig, Gerhardt G.en
dc.contributor.departmentBiologyen
dc.date.accessioned2014-03-14T21:23:24Zen
dc.date.adate2006-12-14en
dc.date.available2014-03-14T21:23:24Zen
dc.date.issued1994-09-01en
dc.date.rdate2006-12-14en
dc.date.sdate2006-12-14en
dc.description.abstractMacrophages (Mφ) are a major immune cell involved in anti-tumor responses. Mφ activities such as tumor cytotoxicity. presentation of tumor-associated antigens, and stimulation of anti-tumor lymphocytes are all involved in the battle against tumor growth. However, other Mφ activities such as cell growth promotion, angiogenesis, and suppression of anti-tumor lymphocytes aid in tumor growth. This dissertation discusses how tumors control Mφ activities to create favorable environments for tumor growth. Assessment of tumor- and Mφ-derived molecules has enabled me to design models of communication between tumors, Mφ, and other immune cells. A major research focus was to determine how tumor-derived molecules induce Mφ suppressor activity and control Mφ cytotoxicity. Tumor growth induced Mφ to suppress T lymphocyte proliferation by increasing Mφ production of the suppressor molecules prostaglandin E₂ (PGE₂), nitric oxide (NO), and tumor necrosis factor-α (TNF-α). A major finding was that TNF-α's normal up-regulatory action on T-cell proliferation switched to a suppressor action when Mφ were present. The autocrine action of increased TNF-α levels during tumor growth stimulated Mφ PGE₂ and NO synthesis, which suppressed T-cell proliferation.en
dc.description.degreePh. D.en
dc.format.extentxxiv, 404 leavesen
dc.format.mediumBTDen
dc.format.mimetypeapplication/pdfen
dc.identifier.otheretd-12142006-131852en
dc.identifier.sourceurlhttp://scholar.lib.vt.edu/theses/available/etd-12142006-131852/en
dc.identifier.urihttp://hdl.handle.net/10919/40420en
dc.language.isoenen
dc.publisherVirginia Techen
dc.relation.haspartLD5655.V856_1994.A545.pdfen
dc.relation.isformatofOCLC# 32749727en
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject.lccLD5655.V856 1994.A545en
dc.subject.lcshMacrophagesen
dc.subject.lcshTumors -- Growthen
dc.titleRegulation of macrophage activities by tumor growth: mechanisms of immunosuppressionen
dc.typeDissertationen
dc.type.dcmitypeTexten
thesis.degree.disciplineBiologyen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.namePh. D.en

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