William S. and Lois Stiles Edgerly Professor of Neurology and Professor of Immunobiology; Chair, Department of Neurology; Neurologist-in-Chief, Yale New Haven Hospital
Understanding the Anti-Tumor Immune Response
Glioblastoma multiforme (GBM) is the highest-grade primary brain tumor and the most common and aggressive form of brain cancer with a prevalence of 2-3 cases per 100,000 subjects in Europe and North America. There are no effective treatments for these tumors and present treatment involves gross total resection of the tumor followed by chemo and radiotherapy. However we are not much more successful at treating glioblastoma tumors than we were 5 or 10 years ago. Glioblastoma tumors are highly infiltrative and have microscopic extensions in the brain surrounding the tumor mass that cannot be removed by surgical means without sacrificing unacceptable amounts of normal brain tissue. Therefore glioblastoma tumors recur and despite treatment, the median survival is only 14 months.
It has been shown that an inflammatory response is launched against glioblastoma tumors in the brain and while T cells have been shown to enter the tumor microenvironment, they are ineffective in clearing the tumor. This suggests that the immune system is suppressed in the local tumor environment, potentially by suppression of effector T cells or local tolerance to the tumor cells.
My work in the lab is focused on understanding the mechanisms behind this suppression of the anti-tumor immune response. I am interested in investigating the manipulated phenotypic and functional changes of the infiltrating immune cells in the tumor microenvironment to further our knowledge of their basic cell biology and identify the important pathways that could be targeted in future therapeutics.
Understanding how tumors mediate this immune suppression is an important step towards designing new therapeutics to complement or even eventually replace today’s unsatisfactory options. For this aim we require much more knowledge about the immune responses to cancer as research directed to and targeting the cancer alone has thus far proved ultimately unsuccessful.