Esophageal cancer remains a challenging disease due to limited treatment options and poor prognosis. In recent years,
immune checkpoint inhibitors (ICI) have been proven to be safe and effective in the treatment of highly lethal
malignancies, such as
non-small cell lung cancer and
melanoma. Recent clinical trials also showed promising activity in
immune checkpoint inhibitors in pretreated advanced esophageal
carcinoma and a potentially significant impact on the outcome of selected patients, independently of histology. Combination studies evaluating
immunotherapy and
chemotherapy and, in localized disease,
radiotherapy are in progress and will hopefully confirm their promises in the near future. However, reliable predictive
biomarkers are still lacking. Indeed, at present, the role of programmed cell death
ligand 1 expression and other factors (such as
microsatellite instability and
tumor mutational burden) as predictive
biomarkers of benefit to
immune checkpoint inhibitors is still controversial. Our aim was to explore the rationale of ICIs in
esophageal cancer, review the results already available in multiple settings, and investigate future perspectives with single-agent and combination strategies.