Immune co-signaling to treat cancer

The past two decades have been marked by a growing understanding of the co-stimulatory and co-inhibitory pathways that are critical to the generation of an effective, well-regulated immune response. Capitalizing on an increasingly nuanced appreciation for the role that these molecules play in anti-tumor immune responses, a diversity of novel therapies to treat human cancers are being explored. The ground-breaking success of anti-CTLA-4 therapy in the treatment of advanced melanoma has set the stage for the clinical development of agents targeting a diversity of co-stimulatory and co-inhibitory molecules. Herein, we review the co-signaling molecules that regulate T cell activation with a focus on their potential role(s) in anti-tumor immune responses. Where available, pre-clinical and clinical studies evaluating the anti-tumor activity of agents targeting these molecules are presented.