“This results in T-cell activation, which propagates an inflammatory reaction. But, just like any other process in the body, once this process starts, at some point it needs to stop; otherwise, the process will continue unchecked, leading to autoimmune disorders,” said Dr. Kim. T-regulatory (T-reg) cells express PDL-1, which binds to a PD-1 receptor on the T cell, inhibiting the T cell and stopping the inflammatory response. Tumors tend to “kidnap” the body’s normal mechanisms, however. The immune system recognizes a tumor cell as foreign, and sends lymphocytes to infiltrate it and mount a cytotoxic reaction. Tumor cells respond by producing PD-1 to bind to the receptor on the T cells and turn them off.
“The argument for immunotherapy is that if you can break this reaction, by utilizing either an antibody against the ligand or the receptor of the PD1/PD-L1 pathway, it will reactivate those T cells, leading to the T cells mounting a cytotoxic reaction against the tumor cells,” he said.
Two immunotherapies are currently approved for use as second-line agents in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) who have failed the standard EXTREME regimen of cetuximab, cisplatin or carboplatin, and 5-FU: nivolumab (Opdivo) and pembrolizumab (Keytruda).