Immune restoration in head and neck cancer patients via cyclooxygenase inhibition: an update.
Most carcinomas overexpress cyclooxygenase, especially COX-2, thus secreting large amounts of immunosuppressive prostaglandins. Epidemiological data and animal models have provided evidence that inhibition of cyclooxygenase and thus prostaglandin E2 synthesis via non-steroid antiinflammatory drugs (NSAIDs) inhibits tumor growth in vitro and in vivo. Moreover, it could be demonstrated that chemoprevention, i.e. the long-term use of NSAIDs, significantly reduced the risk of developing certain types of cancer. However, the molecular mechanisms underlying these antineoplastic effects are not entirely understood. This review focuses on prostaglandin-mediated immunosuppressive mechanisms in head and neck cancer and presents immunorestorative strategies via cyclooxygenase inhibition in vitro and in vivo with special emphasis on COX-2. A better understanding of the interaction of tumors with the immune system and how the process of carcinogenesis can be antagonized by selectively modulating the activity of specific enzymes such as COX-2 will provide the rationale for the use of NSAIDs for chemoprevention or immunoadjuvant cancer therapies.
Lang
S
S
Department of Otorhinolaryngology, Head and Neck Surgery, Ludwig-Maximilians-University of Munich, Munich, Germany. stlang@hno.med.uni-muenchen.de
Zeidler
R
R
D000818:Animals; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007166:Immunosuppressive Agents; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases