Investigating the Immunotherapeutic Potential of Esophageal Cancer

The incidence of patients diagnosed with esophageal cancer is estimated at approximately 17,000 in the United States and 456,000 worldwide every year. Approximately, 85% of these patients will succumb to their disease. Current treatment consists of neoadjuvant chemoradiotherapy followed by esophagectomy (when feasible) in patients with locally advanced disease. Patients with metastatic disease are given palliative chemotherapy with recent studies evaluating molecular targets. Given the disappointing results with targeted therapies in these patients, there has been growing interest in novel therapeutic strategies. KEYNOTE-28, a Phase 1B clinical trial, is evaluating the use of PD-1 inhibition in patients with PD-L1 expressing gastroesophageal tumors, finding a 30% and 40% response rate in squamous cell and adenocarcinoma of the esophagus, respectively. Coincidently, our group’s recent analysis of the cancer genome atlas has found that high mRNA co-expression of immunosuppressive checkpoints, indoleamine 2,3 dioxygenase 1 (IDO1), PD-1 and/or PD-L1, associated with decreased survival in patients with esophageal cancer. These observations form the basis for further understanding of the expression, role and targetability of immune checkpoints for immunotherapy of esophageal cancer.