The NIH has awarded a five-year, $2.79 million R01 research grant to Justin Milner, PhD, a UNC Lineberger member and assistant professor in the department of Microbiology and Immunology in the UNC School of Medicine.
Cancer fighting T cells become dysfunctional in the tumor microenvironment, blunting immunotherapy responses. Milner’s project seeks to define how a druggable family of epigenetic regulators control T cell activity, which may provide insight into new therapeutic approaches for boosting T cell responses in infection and cancer.
In cancer and chronic infection, CD8 T cells differentiate into an epigenetically distinct, dysfunctional lineage referred to as exhausted T cells. Milner’s group has identified unexpected roles for the bromodomain and extraterminal domain (BET) family of proteins in coordinating T cell differentiation and exhaustion. Justin plans to blend immunological, molecular, genetic, and pharmacological approaches to manipulate the activity of BET proteins in CD8 T cells. He will investigate whether newly developed inhibitors of BET proteins can be used to prevent or reverse T cell exhaustion.
According to Milner, “Resolving the roles of BET proteins in exhaustion has broad implications for understanding fundamental epigenetic control of T cell differentiation and the immunological consequences of BET inhibitors.” He is hopeful this work will reveal new, promising strategies for genetic or pharmacological reprogramming of T cell exhaustion, and he is especially interested in boosting T cell responses in the context of pancreatic cancer.
—Tyler Rice, UNC Lineberger Pancreatic Cancer Center of Excellence