Mayo Clinic researchers identify cell cue for destroying tumors

ROCHESTER, Minn. -- Mayo Clinic researchers have identified and characterized an important signal used by the human immune system to help destroy tumors. When this signal is generated inside cells called natural killer (NK) cells, materials are released in the body that induce cell death in cancer cells. Now that this signal has been identified, new strategies can be generated for enhancing the ability of the immune system to kill tumor cells in patients with cancer.

Their report appears in the April 2 online edition of Nature Immunology (http://www.nature.com/natureimmunology). The Mayo Clinic team describes findings on causes that initiate natural killer cells' specific toxic response to tumors or viruses.

Significance of the Mayo Clinic Research

The Mayo Clinic group identified a new signaling mechanism by which natural killer cells initiate a toxic response against cancers and viruses -- an important piece of information when designing therapies that stop, reverse or protect against cancer. Natural killer cells are blood cells that have an innate ability to kill tumor cells and virus-infected cells. For example, when an NK cell encounters a new tumor developing, it may generate signals that will kill the tumor and clear it from the body. However, depending on the signals it receives, it may also communicate the opposite message -- and promote disease -- by generating signals that block the destruction of tumors or viruses.

While scientists have known that NK cells play key roles in fighting cancer, no one has known precisely how the NK cells initiate these varied tasks. The Mayo Clinic work clarifies this by identifying the biochemical players and their role in activating the toxic response against tumor cells and viruses. The Mayo Clinic team discovered a multistep process in which the proteins DAP10, PI-3K and Grb2 must interact with a structure on NK cells called NKG2D. Once that happens, NKG2D can initiate a toxic anticancer response.

"Because NK cells can communicate different messages -- one that serves health by clearing tumors and viruses and one that serves disease by blocking the response to cancer -- understanding which signals result in effective tumor clearance is a high priority for those of us fighting cancer," explains Paul Leibson, M.D., Ph.D., the Mayo Clinic immunologist and pediatrician who led the study.

Collaboration and Support

Together with Dr. Leibson, the work was spearheaded by M.D.-Ph.D. student Jadee Upshaw. The Mayo research team also included Laura Arneson, Renee Schoon, Christopher Dick and Daniel Billadeau, Ph.D. Their work was funded by Mayo Clinic and the National Institutes of Health.

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