Immune checkpoint inhibitors for esophageal squamous cell carcinoma: a narrative review

Esophageal cancer (EC) has the seventh highest incidence and the sixth highest mortality rate of any type of cancer worldwide. In China, esophageal squamous cell carcinoma (ESCC) accounts for more than 95% of EC patients. The main treatment for EC patients is surgery and/or chemoradiotherapy (CRT). A large proportion of EC patients are already at an advanced stage of the disease by the time they are diagnosed. In these cases, CRT is left as the only treatment choice, and the treatment outcome is poor. Immune checkpoint inhibitors (ICIs) can improve clinical response and patient survival of patient with many types of tumors through reactivating antitumor immune response. The study of ICIs in ESCC is relative delayed compared with that in other solid tumors. Recent results from clinical trials have demonstrated the safety and efficacy of ICIs either alone or combined with chemotherapy or chemoradiotherapy in ESCC patients. Accumulated evidences also have shown the improved treatment outcome was associated with PD-L1 expression, tumor DNA instability-induced tumor mutational burden (TMB), and drawing lymphocytes into the tumor. Based on these findings, ICIs combined with CRT or radiotherapy (RT) are the focus of ongoing studies. This review will summarize the recent progress in this field, especially the mechanism of ICIs used in ESCC, their clinical efficacy and toxicities, and potential biomarkers.