Regulation of macrophage activities by tumor growth : mechanisms of immunosuppression
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Macrophages (MÃ¸) are a major immune cell involved in anti-tumor responses. MÃ¸ 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 MÃ¸ activities such as cell growth promotion, angiogenesis, and suppression of anti-tumor lymphocytes aid in tumor growth. This dissertation discusses how tumors control MÃ¸ activities to create favorable environments for tumor growth. Assessment of tumor- and MÃ¸-derived molecules has enabled me to design models of communication between tumors, MÃ¸, and other immune cells. A major research focus was to determine how tumor-derived molecules induce MÃ¸ suppressor activity and control MÃ¸ cytotoxicity. Tumor growth induced MÃ¸ to suppress T lymphocyte proliferation by increasing MÃ¸ production of the suppressor molecules prostaglandin E2 (PGE2), nitric oxide (NO), and tumor necrosis factor-Î± (TNF-Î±). A major finding was that TNF-Î±'s normal up-regulatory action on T-cell proliferation switched to a suppressor action when MÂ¢ were present. The autocrine action of increased TNF-Î± levels during tumor growth stimulated MÃ¸ PGE2 and NO synthesis, which suppressed T-cell proliferation.
- Doctoral Dissertations