Understanding Why The Anti-Cancer Drug, Pembrolizumab, Fails In Certain Patients

Head and neck squamous cell carcinoma (HNSCC) is attributed to tens of thousands of deaths annually and more effective treatments are needed. Pembrolizumab (Pembro), an immunomodulatory PD1-inhibitor drug, acts to prevent tumors from inactivating proximal T cells which often results in rapid T cell-mediated tumor regression. However, Pembro has paradoxically led to rapid growth in the lab’s HNSCC cell lines that have a known JAK-STAT pathway mutation. The study’s goal was to better understand the molecular basis of how Pembro counterintuitively promotes cancer, given this mutation. It was hypothesized that T cells, activated by the presence of Pembro, release cytokines, activating the mutated JAK-STAT pathway in the cancer cells, leading to proliferation. The findings demonstrate that the combination of both Pembro and T cells causes an increase in pSTAT3 production and subsequent overactivation of the JAK-STAT pathway and its proliferative effects in HNSCC. The results hint at the potential necessity to check for this JAK-STAT mutation in patients before administration of Pembrolizumab as a cancer drug.