Gut γδ T cells as guardians, disruptors, and instigators of cancer

Colorectal cancer is the third most common cancer worldwide with nearly 2 million cases per year. Immune cells and inflammation are a critical component of colorectal cancer progression, and they are used as reliable prognostic indicators of patient outcome. With the growing appreciation for immunology in colorectal cancer, interest is growing on the role gamma delta T cells have to play, as they represent one of the most prominent immune cell populations in gut tissue. This group of cells consists of both resident populations-gamma delta intraepithelial lymphocytes (gamma delta IELs)-and transient populations that each has unique functions. The homeostatic role of these gamma delta T cell subsets is to maintain barrier integrity and prevent microorganisms from breaching the mucosal layer, which is accomplished through crosstalk with enterocytes and other immune cells. Recent years have seen a surge in discoveries regarding the regulation of gamma delta IELs in the intestine and the colon with particular new insights into the butyrophilin family. In this review, we discuss the development, specialities, and functions of gamma delta T cell subsets during cancer progression. We discuss how these cells may be used to predict patient outcome, as well as how to exploit their behavior for cancer immunotherapy.