The immune system is capable of fighting cancer. Unfortunately, the immune response within tumor tissue is strongly suppressed. My research focuses on understanding the ways by which the immune system is suppressed in tumor tissue, with a specific focus on CD8+ T cells that are key mediators of anti-tumor immunity. The overarching goal of the work in my laboratory is to identify means to empower the immune system to successfully combat cancer. To achieve this, my laboratory employs a multi-disciplinary approach that combines insightful study of the immune system in experimental models, cutting-edge genomics technologies, application of mathematical modeling to data analysis, and translational studies with human tumor specimens. Using this approach, I have challenged existing paradigms and thus uncovered novel receptors that can be harnessed for immunotherapy, described different subsets of intra-tumoral CD8+ T cells that have different functional properties and their underlying genetic differences, discovered how intra-tumoral CD8+ T cells change during a successful response to immunotherapy, and identified signals that are uniquely present inside tumor tissue and influence the functional properties of intra-tumoral CD8+ T cells.
Current and future research questions include examination of how CD8+ T cells communicate with and are influenced by other cells in tumor tissue using tissue imaging and technologies for spatial mapping and the discovery of targets that will simultaneously improve CD8+ T cell responses while mitigating the autoimmune-like toxicity that is often observed in patients being treated with immunotherapy. The latter takes advantage of my unique background in autoimmune disease research. Thus far, my discoveries and expertise have helped bring five immunotherapies into clinical trials and two to registration as investigational new drugs. With the support of the BWH President’s Scholar Award, I will continue to challenge paradigms and break new ground to bring new therapeutic options to patients.