New Tumor Defense System Discovered

As a result, new strategies that decrease the amount of fatty acids around the tumors may provide new approaches to anticancer treatment.

Several types of anticancer therapy are based on immunotherapeutic anti-cancer strategies, therapies that boost the body's immune system, such as cytotoxic T lymphocytes, to help destroy tumors. However, immunotherapeutic techniques are frequently not effective at removing established tumors for a variety of reasons including a loss of the ability of the cytotoxic T lymphocytes to recognize the tumor and a physical barrier separating the tumor and the lymphocytes.

Now, researchers from the Torrey Pines Institute for Molecular Studies (San Diego, CA, USA) have added another reason to this inventory. They found that tumors secrete fatty acids which suppress the cytotoxic T lymphocytes' ability to destroy tumor cells. Their findings were published in the September 2005 issue of the Journal of Lipid Research.

"We found two things,” explained Dr. Alan M. Kleinfeld. "First, the most common type of free fatty acids, which at normal levels are essential for life, at high levels prevents the cytotoxic T lymphocytes from destroying tumor cells. The second thing is that human breast cancer cells, but not normal tissue from the same breast, produce very large amounts of the type of free fatty acids that block the cytotoxic T lymphocytes. Thus, the cancer may have a way of defending itself against attack by the immune system, thereby reducing the potential efficacy of novel anti-cancer therapies that rely on a functioning immune system.”

The free fatty acids work against cytotoxic T lymphocytes by inhibiting a number of the lymphocytes' signaling processes. For example, they keep specific proteins from being phosphorylated and they also prevent an increase in intracellular calcium that is vital for the cytotoxic T lymphocytes to destroy the tumor cells. Dr. Kleinfeld believes that these signaling mechanisms are being blocked at the cells' membranes.

These findings raise the possibilities of new therapeutic targets for cancer, such as those that may move free fatty acids out of the tumor. Furthermore, free fatty acid levels in the blood could be utilized to help evaluate the aggressive potential of a tumor.






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Torrey Pines Institute for Molecular Studies