Title page for ETD etd-12142006-131852
|Type of Document
||Alleva, David G.
||Regulation of macrophage activities by tumor growth : mechanisms of immunosuppression
|Elgert, Klaus D.
|Ahmed, S. Ansar
|Burger, Carol J.
|Lederman, Muriel L.
|Schurig, Gerhardt G.
- Tumors Growth
|Date of Defense
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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