The majority of patients with esophageal cancer present with advanced disease and chemotherapy is the mainstay of palliation. However, efficacy is limited by the development of chemotherapy resistance and treatment options beyond first- and second-line treatment are scarce. Immunotherapy is a novel treatment option that has shown encouraging efficacy in several types of cancer, also in esophageal cancer. In esophageal squamous cell cancer (ESCC), early phase evaluation of immune checkpoint inhibitors has yielded promising results, however, results from phase 3 trials are currently still lacking. Besides checkpoint inhibitors, other immunogenic approaches e.g. peptide vaccines, adoptive T-cell therapy and oncolytic viruses are under development. This review describes the biological rational for immunotherapy and provides first accumulating data on its use in advanced esophageal cancer, with a focus on ESCC.

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