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Lab study defines and blocks mechanism that lets brain tumors sidetrack immune response

LOS ANGELES (Oct. 22, 2004) Researchers at Cedars-Sinai's Maxine Dunitz Neurosurgical Institute have described an immune-disruptive process driven by an enzyme that is overexpressed in the cells of many types of tumors, including malignant brain tumors called gliomas.

Blocking the enzyme's expression in laboratory tests interrupted the series of cell-level events and led to the development of cells capable of launching an immune response. This finding supports the suggestion that medications attacking the enzyme may boost the immune system's ability to recognize and target gliomas.

Results of the study on cyclooxygenase-2 (COX-2) appear in the October 1 issue of the Journal of Immunology. While COX-2 inhibition has been considered an attractive anti-cancer strategy, results of earlier studies on a variety of tumors have been inconsistent, puzzling and sometimes seemingly contradictory. Furthermore, because COX-2 is a complex enzyme that is affected by a variety of conditions and biochemical substances, many of its mechanisms and effects are not clearly understood.

In the article, Institute researchers describe COX-2's detrimental influence on dendritic cells the immune system cells responsible for detecting foreign matter and eliciting an immune response. Dendritic cells, highly specialized "antigen-presenting cells," pick up debris left behind when cells die. When they take up and process debris from tumor cells, they should present these antigens to cytotoxic T lymphocytes (CTL), cancer killing cells, instructing them to attack the tumor cells.

If functioning properly, the dendritic cells would induce the production of a protein called interleukin-12 (IL-12), which prompts the immune system's CD4+ T lymphocytes to launch a T helper type 1 (Th1) response attack mode. Lymphocytes would swarm to the source of the antigens and attack the tumor cells.

Instead, the researchers found, COX-2 and a hormone-like substance it synth
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Contact: Sandra Van
sandy@vancommunications.com
1-800-880-2397
Cedars-Sinai Medical Center
22-Oct-2004


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