Monday, July 2, 2012

Study finds a new potential explanation for why the body can't fight tumors on its own


A study in the journal PLoSOne has identified a completely novel function for a previously known molecule, which may finally shed light on why the body's natural immune system does not attack and destroy cancer cells on contact. The protein, protocadherin-18 (pcdh18), is most often found and commonly associated in neurological functions.

The research, led by the New York University Langone School of Medicine with support from Children's National Medical Center, finds that this protein, which has been identified in CD8+ white blood cells, or so called "killer" white blood cells, plays a significant role in how these key components of the body's immune response to foreign bodies react and respond to tumor cells.

It is the first study to discover that this pcdh18 protein impacts how the body's natural immune system fights (or fails to fight) tumors. In the study, pcdh18 on the CD8+ cells interacts with molecules on the tumor surface, and this interaction inhibits the white blood cell's killer instinct to target and destroy the tumor. The interaction between pcdh18 and the tumor's molecules causes these killer white blood cells to lose their potency, and renders them ineffective in combating the tumor.

The laboratories of Alan Frey, PhD, at NYU, were the primary home for this research, with support and collaboration from investigators in the Immunology Initiative of the Sheikh Zayed Institute for Pediatric Surgical Innovation at Children's National Medical Center, led by Sasa Radoja, PhD.

Researchers have worked for many years to identify what it is about a tumor's genetic and proteomic makeup that allows it to slip past the body's natural defenses. This study is the first to attribute the white blood cells inability to fight the tumor to this specific protein's reaction to the tumor surface. It brings scientists one step closer to finding out why the body's natural immunity is not able to effectively seek and destroy tumor cells.

Next, these teams will work to understand the mechanisms of these protein interactions better, but also, the Immunology Initiative will begin preliminary translational research aimed at exploring ways to avoid the suppression, and possibly open the door for CD8+ white blood cells to zero in on tumors and effectively attack them.

"Our whole research program in Immunology at the Sheikh Zayed Institute is focused on finding ways to alter the function of white blood cells," said Dr. Radoja, co-author of the study. "We want to see how we can change these white blood cells to make them better, stronger, more robust tumor killers."

Read the full study here.