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Regulation of macrophage activities by tumor growth: mechanisms of immunosuppression

Macrophages (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. / Ph. D.

Identiferoai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/40420
Date14 December 2006
CreatorsAlleva, David G.
ContributorsBiology, Elgert, Klaus D., Ahmed, S. Ansar, Lederman, Muriel L., Burger, Carol J., Schurig, Gerhardt G.
PublisherVirginia Tech
Source SetsVirginia Tech Theses and Dissertation
LanguageEnglish
Detected LanguageEnglish
TypeDissertation, Text
Formatxxiv, 404 leaves, BTD, application/pdf, application/pdf
RightsIn Copyright, http://rightsstatements.org/vocab/InC/1.0/
RelationOCLC# 32749727, LD5655.V856_1994.A545.pdf

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