Cell-specific and context-dependent effects of GITR in cancer, autoimmunity, and infection.

A breadth of studies have demonstrated the importance of GITR-GITRL in diverse immune processes. However, only a limited number of studies to date have attributed the effects of GITR/GITRL to specific cell types. Moreover, the context-dependent role of GITR/GITRL in different models makes the consequences of GITR ligation difficult to generalize. There is a significant interest in the therapeutic application of GITR agonists and antagonists in human disease. Thus, the field must come to a consensus regarding the cell type-specific and physiological effects of GITR in different disease states. Here we attempt to summarize the extensive literature on GITR, to synthesize a more cohesive picture of the role of GITR/GITRL in immunity, and to identify areas that require clarification.