Researchers Discover New Tumor Defense System

Several forms of anti-cancer therapy rely on what is known asimmunotherapeutic anti-cancer strategies, therapies that encourage thebody's natural defenses, such as cytotoxic T lymphocytes, to aid indestroying tumors. However, immunotherapeutic methods are often noteffective at removing established tumors for a number of reasonsincluding a loss of the ability of the cytotoxic T lymphocytes torecognize the tumor and a physical barrier separating the lymphocytesand the tumor.

Now, Dr. Alan M. Kleinfeld and Clifford Okada of the TorreyPines Institute for Molecular Studies in San Diego, CA, have addedanother reason to this list. They discovered that tumors secrete fattyacids which inhibit the cytotoxic T lymphocytes' ability to kill tumorcells.

"We found two things," explains Dr. Kleinfeld. "First, the mostcommon type of free fatty acids, which at normal levels are essentialfor life, at high levels prevents the cytotoxic T lymphocytes fromdestroying tumor cells. The second thing is that human breast cancercells, but not normal tissue from the same breast, produce very largeamounts of the type of free fatty acids that block the cytotoxic Tlymphocytes. Thus the cancer may have a way of defending itself againstattack by the immune system, thereby reducing the potential efficacy ofnovel anti cancer therapies that rely on a functioning immune system."

The free fatty acids act against cytotoxic T lymphocytes byblocking a number of the lymphocytes' signaling events. For example,they keep certain proteins from being phosphorylated and they alsoprevent an increase in intracellular calcium that is essential for thecytotoxic T lymphocytes to kill the tumor cells. Dr. Kleinfeld suspectsthat these signaling events are being blocked at the cells' membranes.

These results from the Torrey Pines Institute for MolecularStudies raise the possibilities of new therapeutic targets for cancer,such as those that may transport free fatty acids out of the tumor.Alternatively, free fatty acid levels in the blood could be used tohelp gauge the aggressive potential of a tumor.

The American Society for Biochemistry and Molecular Biology (ASBMB)is a nonprofit scientific and educational organization with over 11,000members in the United States and internationally. Most members teachand conduct research at colleges and universities. Others conductresearch in various government laboratories, nonprofit researchinstitutions, and industry.

Founded in 1906, the Society is based in Bethesda, Maryland, onthe campus of the Federation of American Societies for ExperimentalBiology. The Society's primary purpose is to advance the sciences ofbiochemistry and molecular biology through its publications, theJournal of Biological Chemistry, the Journal of Lipid Research,Molecular and Cellular Proteomics, and Biochemistry and MolecularBiology Education, and the holding of scientific meetings.

For more information about ASBMB, see the Society's website at www.asbmb.org.

The manuscript for the Journal of Lipid Research paper can be downloaded from the following URL:http://www.jlr.org/cgi/content/abstract/M500151-JLR200