The role of the PD-L1:PD-1 pathway in squamous cell carcinoma of the head and neck

Antigen specific stimulation of immune cells, triggers expression of a diverse array of co-signaling molecules that help define the fate of the resultant immune response. Antibodies and fusion proteins, capable of blocking and/or activating these co-signaling pathways, are emerging as potent therapeutic options for the treatment of cancer and autoimmune disease. Blockade of one such pair of co signaling interactions, termed PD-L1:PD-1, has shown tremendous promise in phase I treatment trials for advanced solid tumors like non-small cell lung cancer and melanoma, with long term disease remission in select patients. Based on intriguing preclinical data from our group and others, several trials are actively evaluating the utility of PD-L1:PD-1 blockade for the treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN). In this review we will explore what is known about the interactions between PD-1 and PD-L1, with a focus on SCCHN, and specifically discuss how this pathway can be manipulated with therapeutic intent.