November 12, 2008
Investigating how tumors play hide-and-seek
ATLANTA — The body’s immune system is its line of defense against foreign invaders, from viruses to bacteria and tumors. But often tumors find ways to hide from the immune system, making it harder for the body to attack these deadly, swiftly multiplying cells.
Georgia State University’s Susanna Greer, assistant professor of biology and a Georgia Cancer Coalition researcher, received a four-year, $718,000 grant from the American Cancer Society in October to further explore proteins which play a role in allowing the body’s immune system to detect tumors.
Greer, a Georgia Cancer Coalition scientist, examines two proteins called Major Histocompatibility Complex (MHC) classes 1 and 2, which are in every cell of the body with the exception of red blood cells.
Each plays a similar role in bringing parts of foreign invaders like viruses or bacteria that have made it into the body — tipping off the immune system's response. Class 1 typically alerts the immune system of foreign bodies within the cell, and brings pieces of those invaders to the surface.
By contrast, MHC Class 2 works to let the immune system know of foreign bodies in the spaces between cells.
Once alerted, the immune system starts an inflammatory response to clear out the infection — as it would with any foreign body, Greer explained.
“MHC Class 1 expressed on a tumor cell will alert the immune system that there are things inside that tumor cell that are different," she said. "The immune system doesn’t care, because it just sees those cells as different, and will use the attack mechanism to kill the tumor cell.”
The problem is that tumors are good at turning off these proteins that sound the warning.
The American Cancer Society grant is going toward the investigation of a specific mechanism used to create MHC Class 2. Class 2 alerts the immune system to proteins shed by tumor cells in the space between cells, allowing the immune system to attack tumor cells.
The epigenetic code used to make MHCs proteins is very complex and bound into extremely tight packages within genes. Greer and her lab are exploring how this code is translated to regulate the production of MHC Class 2.
Although MHC proteins play important roles in getting the immune system to respond to foreign invaders, sometimes the problem is not that the proteins are kept off — but stay on, causing autoimmune disorders like multiple sclerosis where the immune system attacks the central nervous system. So, discoveries made in protein transcription can open up a new way to help treat not just cancer, but other disorders as well.
“The more that we find out about how these proteins are transcribed and translated, in addition to how you can turn on transcription and turn it off, there are some very relevant chemical applications,” Greer said.