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New Study Points to Novel Mechanism by Which Tumors Escape Recognition by the Immune System
Date:11/29/2011

IRVING, Texas, Nov. 29, 2011 /PRNewswire/ -- A new study in The Journal of Clinical Investigation (JCI) has uncovered a novel mechanism that cancer cells may use to escape detection by the body's immune system. The study, "Tumor-infiltrating myeloid cells induce tumor cell resistance to cytotoxic T cells in mice," led by researchers at the H. Lee Moffitt Cancer Center in Tampa, Fla., shows that a specific type of immature white blood cells (myeloid derived suppressor cells or "MDSCs") are recruited to tumors where they modify tumor cells so that they are no longer recognized by the immune system's cells (cytotoxic T cells) that fight cancer. The study also suggested that bardoxolone methyl, the lead compound in a new class of molecules called antioxidant inflammation modulators (AIMs), may have the ability to prevent these modifications and thereby boost the immune system's ability to detect and fight cancer.

In previous studies, the authors, Dr. Dmitry Gabrilovich and colleagues, showed that oxidative stress produced by MDSCs inhibited tumor recognition by the immune system (Nature Medicine, 2007). The findings in the new study demonstrate how this occurs. Oxidative stress produced by MDSCs alters the surface proteins on tumor cells so that cytotoxic T cells can no longer recognize the tumor. The authors hypothesized that reducing oxidative stress in the tumor microenvironment would prevent alteration of tumor surface proteins and thereby restore the immune system's ability to recognize the tumor. The authors chose to use one of Reata's AIM class compounds to lower oxidative stress because it is a potent activator of Nrf2 and inhibitor of NFκB, thereby reducing oxidative stress and suppressing inflammation. In mice with lung cancer or melanoma, treatment with the AIM improved the ability of cytotoxic T cells to recognize tumor cells and significantly slowed tumor growth. This approach may be important in addressing other tumor ty
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SOURCE Reata Pharmaceuticals
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