The Cancer Research Institute has awarded a five-year STAR program grant of $1.25 million to Haydn T. Kissick, PhD, assistant professor in the Department of Urology at the Emory School of Medicine and cancer immunology researcher at Emory’s Winship Cancer Institute to research how T cells can help protect the body against cancer.
When T cells infiltrate into a tumor, it increases the chances of survival and response to therapy in almost every type of cancer, but different patients have different levels of T cells, even in a single tumor type, from almost none to more than 20 percent. In particular, the Kissick lab is studying a cytotoxic subset called CD8 T cells, searching for the genetic signaling mechanism that could cause them to target only cancer cells.
“A T-cell is unable to just find a cancer cell and kill it,” Kissick explains. “It has to get very specific instructions from other immune cells so that it can do the right thing. If the signals that tell the stem cell to do the right thing and kill the cancer aren’t correct, the immune response breaks down. So it’s an orchestration of many cells working together.”
Kissick’s research will use a two-pronged strategy. One project will systematically knock out hundreds of different genes in mice, one by one, using the process of elimination to see which ones tell the CD8 stem cell to become a cancer killer. The second project will administer a drug to prostate cancer patients at Emory Healthcare designed to activate all the immune cells in their tumor at once. They’ll then analyze samples of those tumors in the lab to see if the same gene is present in the human tissue.
A separate but parallel project will look at the relationship between CD8 T cells and a different subset, CD4 T cells, the so-called “helper cells” which can turn on the CD8 cells so they target cancers. Kissick hopes this might be an alternative path to control immune response. “The CD4 T cells are higher up in the food chain,” he says. “They send signals down. We’ll use the CD4 T cell to instruct the CD8 T cell what to do. A good place for us to make drugs to intervene in those communications, that can tell the immune system to kill the cancer better.”