Lymphocyte Activation Gene 3 (LAG-3)

Lymphocyte activation gene 3 (LAG-3, CD223) is a protein expressed on the surface of activated T cells, regulatory T cells (Treg), natural killer (NK) cells, B cells, and plasmacytoid dendritic cells. LAG-3 signaling inhibits T cell activation and enhances regulatory T cell function (Camisaschi et al. 2010; Grosso et al. 2007; Joosten et al. 2007; Park et al. 2012). Like other molecules such as cytotoxic T lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and T cell immunoglobulin mucin-3 (TIM-3), LAG-3 has attracted interest in oncology for its role as a negative regulator of T cell activation - an immunological "checkpoint" - that may play a role in helping tumors evade effective immune surveillance. This chapter will present a brief discussion of the molecular structure and biologic function of LAG-3 as a therapeutic target. The current role of LAG-3 in cancer with attention to pertinent preclinical and clinical data will be described. Finally, the potential impact and future directions of research into the optimal use of LAG-3 as a therapeutic target will be presented.