Cancer is on the rise globally with the number of new cancer cases expected to reach 19 million by 2025. In particular, the incidence of cancer is on the rise in industrialized nations. This has been attributed in part to chronic exposure to occupational/environmental irritants that promote cancer-causing inflammation. Center researchers are actively working on how to best target immune checkpoint receptors, a class of molecules whose function is to diminish inflammation, for the treatment of cancer. This is currently one of the most promising areas in cancer immunotherapy and will likely transform cancer care over the next decade.
The Anderson Lab’s research at the Evergrande Center examines how chronic inflammation can cripple the ability of immune system T cells to attack tumor cells. Chronic inflammation leads to an increase in inhibitory receptors on T cells, terminating the cell’s immunological attack on tumors. This termination is known as T-cell “exhaustion” and is effected by reduced expression of those genes responsible for destroying tumor cells. Dr. Anderson’s past research has described the process of T cell exhaustion and an associated regulatory T cell type that exists only in tumor tissue.
In their research at the Evergrande Center, the Anderson Lab constructs detailed models of the highly complex interactions among T cells, tumors, and gene expression, describing the process of exhaustion as T cells become incapable of fighting cancer. The lab’s description of the mechanisms behind T cells’ failure to purge cancer cells in individuals with chronic inflammation will form the basis of future therapeutic interventions.
The Sharpe Lab is examining the functions of key immunoregulatory pathways, known as T cell coinhibitory pathways, which play critical roles in regulating T tolerance and inflammation, and are key mediators of T cell dysfunction in cancer, chronic infections and autoimmunity. T cell coinhibitory pathways normally control inflammatory responses in tissues and protect tissues from autoimmune attack. However, tumors have usurped these pathways to evade eradication.
In their research at the Evergrande Center, the Sharpe Lab is exploring mechanisms by which PD-1 and other coinhibitory pathways exert their immunosuppressive effects in tissues. The Sharpe lab will use transcriptomic approaches to investigate mechanisms by which T cell coinhibitory pathways, individually and together, regulate tissue tolerance and inflammation. The Evergrande Bioinformatics Resource will be beneficial for these studies. One of the areas to be examined will be the cell intrinsic effects of coinhibitory molecules on stromal and tumor cells, which can regulate T cell activation and tolerance. The lab will also define molecular mechanisms by which coinhibitory pathways control functions of T cells, myeloid cells and stromal cells in the tumor microenvironment.