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Penn study shows link between immune system suppression and blood vessel formation in tumors
Date:7/13/2011

PHILADELPHIA - Targeted therapies that are designed to suppress the formation of new blood vessels in tumors, such as Avastin (bevacizumab), have slowed cancer growth in some patients. However, they have not produced the dramatic responses researchers initially thought they might. Now, research from the Perelman School of Medicine at the University of Pennsylvania might help to explain the modest responses. The discovery, published in the July 14 issue of Nature, suggests novel treatment combinations that could boost the power of therapies based on slowing blood vessel growth (angiogenesis).

The Penn investigators, led by George Coukos, MD, PhD, Celso-Ramon Garcia Professor of Reproductive Biology, found that ovarian cancer cells grown under low oxygen conditions which promote blood vessel formation secrete chemical signals that suppress the patient's immune system, preventing it from killing off the abnormal cancer cells.

"For the first time, we are realizing that the two programs angiogenesis and immune suppression are co-regulated and the two programs are mediated by the same cell types," Coukos says. "This creates new therapeutic opportunities, since the study reveals that in order to effectively suppress angiogenesis, one should also suppress a type of immune cell, called regulatory T cells.Thus, commonly used anti-angiogenesis therapies should be combined with therapeutic maneuvers that eliminate regulatory T cells."

Following hints that there might be cross-talk between the two systems, first author Andrea Facciabene, PhD, research assistant professor of Obstetrics and Gynecology, and colleagues grew ovarian cancer cells under normal oxygen conditions or low oxygen (hypoxic) conditions. When the team looked for differences in the proteins called chemokines secreted under the two growth conditions, they found that one signaling molecule, CCL28, was more abundant in low oxygen cultures. CCL28 was also commonly express
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Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

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