Innate and Adaptive Immune Modulation Strategies for Therapeutic Gain

Cancer immune checkpoint therapies are now a standard of care and have shown curative response in a subset of patients. Unfortunately, we are still lacking insight into the mechanisms regulating immunotherapy resistance that must be overcome to make immunotherapies effective broadly for patients and across cancer types. Key factors driving this treatment resistance include an immunosuppressive tumor microenvironment and insufficient effector T cell responses. Our work uses a systems biology approach focusing on two immune modulation strategies to overcome immunotherapy resistance: Targeting myeloperoxidase to counteract an immunosuppressive microenvironment and developing mRNA vaccines to activate and recruit effector T cells into the tumor microenvironment. Our work uses a combination of preclinical tumor models, tumor immunology and intravital imaging studies. We demonstrate that limiting myeloperoxidase alter the tumor-immune microenvironment and significantly enhances immune checkpoint therapy response in preclinical models of melanoma and pancreatic cancer. We also demonstrate the promise of mRNA vaccines as adjuvants to increase immunotherapy outcomes.

Dr. Liu is currently an Assistant Professor in the Department of Microbiology, Immunology, and Cell Biology and a member of the West Virginia University Cancer Institute at West Virginia University (WVU). After obtaining her PhD degree from the University of Toronto, she completed her postdoctoral training at the University of Texas MD Anderson Cancer Center. Dr. Liu’s lab studies tumor-immune cell interactions as it relates to cancer progression and therapeutic response. Current projects include defining the contribution of innate immune cells to an immunosuppressive, understanding treatment resistant tumor microenvironment, and developing immune modulation strategies to enhance anti-cancer immune responses. The lab uses a cutting-edge bioluminescence-fluorescence molecular intravital imaging platform, complemented by a variety of approaches which include, in vivo studies, functional assays, single cell analyses, and immunological techniques. Our research goals aim to provide translatable insight into the impact of the immune system and broader tumor microenvironment to improve cancer detection and therapeutic response.