Title page for ETD etd-12142006-131852


Type of Document Dissertation
Author Alleva, David G.
URN etd-12142006-131852
Title Regulation of macrophage activities by tumor growth : mechanisms of immunosuppression
Degree PhD
Department Biology
Advisory Committee
Advisor Name Title
Elgert, Klaus D. Committee Chair
Ahmed, S. Ansar Committee Member
Burger, Carol J. Committee Member
Lederman, Muriel L. Committee Member
Schurig, Gerhardt G. Committee Member
Keywords
  • Tumors Growth
  • Macrophages
Date of Defense 1994-09-01
Availability restricted
Abstract

Macrophages (Mø) are a major immune cell involved in anti-tumor responses. Mø 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 Mø activities such as cell growth promotion, angiogenesis, and suppression of anti-tumor lymphocytes aid in tumor growth. This dissertation discusses how tumors control Mø activities to create favorable environments for tumor growth. Assessment of tumor- and Mø-derived molecules has enabled me to design models of communication between tumors, Mø, and other immune cells. A major research focus was to determine how tumor-derived molecules induce Mø suppressor activity and control Mø cytotoxicity. Tumor growth induced Mø to suppress T lymphocyte proliferation by increasing Mø 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 M¢ were present. The autocrine action of increased TNF-α levels during tumor growth stimulated Mø PGE2 and NO synthesis, which suppressed T-cell proliferation.

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