Case Western Reserve University School of Medicine has received a $1.6 million grant from the National Cancer Institute (NCI) to study how tumor cells avoid detection by the body's immune system, allowing cancer to develop and spread.
The five-year National Institutes of Health grant will enable researchers led by Alex Y. Huang, MD, PhD, assistant professor of pediatrics, pathology, and biomedical engineering at the School of Medicine, and a hematologist and oncologist at Rainbow Babies & Children's Hospital at University Hospitals Case Medical Center, to examine "immune tolerance." The process keeps tumor cells from being detected by the immune system, even when they invade draining lymph nodes, a place where primary immune activation and surveillance take place. Lymph nodes are part of the body's lymphatic system, which fights off viruses, bacteria, and other disease-causing agents.
The study will also test whether modifying the environment in which tumor and immune cell interactions take place, using a group of proteins called inflammatory chemokines, will activate unresponsive immune cells into fighting off cancer. Using inflammatory chemokines as part of the anti-tumor strategies is a novel approach to cancer treatment.
"This research will provide greater insight into the potential therapeutic utilities of inflammatory chemokines, thereby providing a new direction for the development of immunotherapies that are capable of fighting cancer at the most basic cellular level," Dr. Huang says, who is also an associate member of the Case Comprehensive Cancer Center at the School of Medicine and director of the Pediatric Hematology-Oncology Fellowship Program at Rainbow Babies & Children's Hospital. "Any effective cellular immunotherapy must enhance long-term tumor immunity, effectively concentrating immune cells and priming them to destroy cancer cells anywhere in the body over long periods of time."
Researchers will work to leverage the immune system's unique ability to generate immune memory to eradicate any future cancer cell development that is derived from a primary tumor, according to Dr. Huang. They will use an advanced imaging technique called intravital 2-photon laser scanning microscopy to directly visualize tumor and immune cell interactions in real-time.
Dr. Huang's laboratory has been at the forefront of developing this imaging technology, which he says provides a "court-side" view of how tumors and the immune system interact with one another within intact tissue as cancer spreads to the lymph nodes. The technology is designed to provide a powerful in vivo experimental platform to monitor future anti-cancer or immunotherapy approaches, as opposed to static tissue analysis or single-cell analysis on a plastic petri dish, he explains.
Dr. Huang's research is among the first attempts to directly visualize the tolerance of immune cells by metastatic cancer cells in the draining lymph node at a cellar level, in a dynamic fashion.
As a practicing pediatric hematologist and oncologist, Dr. Huang aims to one day be able to apply the scientific insight gained from this research in a pediatric care setting.
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