Investigators Show How Key Growth Factor Influences Immune System
Gerstner Sloan-Kettering faculty member Joan Massagué and Memorial Sloan-Kettering investigator Dori A. Thomas have published a paper showing how the protein called transforming growth factor-beta (TGF-ß) allows tumor cells to escape killing by the immune system. It does this by suppressing the tumor-killing activities of immune cells called cytotoxic T lymphocytes (CTLs). TGF-ß has been a well-studied cellular protein in cancer research because it can act as either an inhibitor or a promoter of cell growth.
When functioning properly, CTLs recognize tumor cells and destroy them before they have time to grow and spread. The current research, published in the journal Cancer Cell in November 2005, shows that tumors mobilize TGF-ß, and that TGF-ß in turn prevents CTLs from producing factors that kill tumor cells. Using microarray analysis of immune cells in culture, the researchers found about 100 genes whose expression levels were influenced by exposure to TGF-ß. Among those were the genes that encode for the five key proteins in CTLs. [PubMed Abstract]
"Now that we understand this particular function of TGF-ß, we can dig deeper into the molecular mechanisms of how this interaction takes place," said Dr. Massagué, a cancer biologist and the paper's senior author. "Ideally we would like to devise ways to block TGF-ß in this context, and this work provides guidance for the development of new therapies." The paper's first author was Dr. Thomas, an immunologist and a member of Dr. Massagué's laboratory.