T-cells are important in regulating anticancer activity
The immune system is your body’s defense force—it identifies, targets and fights foreign cells in the body to guard against illnesses. But sometimes, cells go rogue and are able to evade the immune system and cause cancer. Versiti Blood Research Institute (BRI) Associate Investigator Matthew Riese, MD, PhD, is studying the immune system and cancer cells, with a goal of figuring out how a patient’s own immune system can be “weaponized” to help fight their cancer.
According to Dr. Riese, the most important weapons an immune system has in regulating anticancer activity are a patient’s T-cells, which are a type of cell that helps get rid of cells that are altered by viral infection or cancer mutations. Specifically, he is most interested in studying cytotoxic T-cells, which are responsible for the direct killing of virally infected cells and cancer cells.
One of the major recent breakthroughs on how cancer evades T-cell killing has been the identification of proteins on the surface of T-cells that block their functionality. In fact, discoveries of the proteins PD1 and CTLA-4 won the 2018 Nobel Prize in Medicine, and researchers have found that when PD1 is blocked, it can induce cancer remission about one-third of the time in many cancers. Dr. Riese said there is a need to find other proteins like these in T-cells to find out if they are good targets to treat cancer.
But how does it all work? When cancer cells mutate, they express foreign peptides, or fragments of proteins that attract attention from T-cells, resulting in the elimination of the cancer cells. T-cells accomplish this task through expression of a T-cell receptor, which is a molecule on the surface of the cell that binds to foreign peptides and triggers T-cell mediated killing. Some rogue cells are able to avoid T-cell mediated killing and become cancer. Dr. Riese wants to make T-cells better able to attack rogue cancer cells.
His research focuses on proteins called diacylglycerol kinases (DGKs), which are proteins made inside T-cells that act as an “off” switch. DGKs are important to limit T-cell inflammation; however, blocking the proteins in patients with cancer has the potential to enhance T-cell elimination of tumors. T-cells that lack DGKs are insensitive to inhibition by PD1 or CTLA-4. Dr. Riese hopes that targeting DGKs will soon move to clinical trials and will be used to treat patients with a variety of cancers. “If you can develop an immunotherapy (using the immune system to treat disease), you can greatly improve patient outcomes,” he said.
In addition to his research lab at Versiti Blood Research Institute, Dr. Riese has an appointment at the Medical College of Wisconsin, where he sees patients with cancers who would greatly benefit from new immunotherapies.
“As a practicing clinician and researcher, I am fortunate because my work covers the full spectrum of activities, from discovering and developing therapeutics to using them to help save lives,” he says. “Normally, clinicians observe an urgent, unmet need for patients and then they have to get a basic scientist interested and address the problem—it can take years. In contrast, I can just take this back to my lab and figure it out.”
Dr. Riese is happy to be part of the BRI’s critical mass of blood health innovators, and finds its collaborative environment helpful for furthering research discoveries. “Increasingly, team science is important in combining expertise to answer questions,” he said. “I feel that the BRI is perfectly suited for that.”
Matthew Riese, MD, PhD, is an associate investigator at Versiti Blood Research Institute and an associate professor in the Department of Medicine, Division of Hematology/Oncology at the Medical College of Wisconsin.