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.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Biology

Department dc:contributor.department

Biology

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

1994

Author dc:creator

• Alleva, David G.

Chair dc:contributor.committeechair

• Elgert, Klaus D.

Committee members dc:contributor.committeemember

• Ahmed, S. Ansar
• Lederman, Muriel L.
• Burger, Carol J.
• Schurig, Gerhardt G.

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Language dc:language.iso

en

Dc Identifier Other

etd-12142006-131852

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/40420