CTLA-4 and its inhibitors in esophageal cancer: efficacy of therapy and potential mechanisms of adverse events.

Esophageal cancer is one of the most prevalent diseases in the world, and its prognosis remains poor. Surgery, chemotherapy, and radiotherapy are the most common treatment strategies for esophageal cancer. Although these conventional treatment methods are sometimes beneficial, patients with esophageal cancer still have a high risk of local relapse and metastasis. Thus, novel and effective therapies are needed. Immune checkpoint inhibitors are a type of immunotherapy being studied as a treatment for patients with advanced cancers, and strategies using such inhibitors have rapidly progressed to be recognized as transformative treatments for various cancers in recent years. Immune checkpoint inhibitors combined with chemotherapy or radiotherapy have become the first-line and second-line treatment strategies for advanced esophageal cancer. In addition, immune checkpoint inhibitors have also been recognized as another option for patients with terminal esophageal cancer who cannot benefit from chemotherapy, and they even have potential benefits as a novel neoadjuvant treatment option for locally advanced esophageal cancer. Currently, there are two types of immune checkpoint inhibitors commonly applied in clinical practice: immune checkpoint inhibitors targeting programmed death 1/programmed cell death ligand 1 and immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated protein 4. However, cytotoxic T-lymphocyte-associated protein 4 immune checkpoint inhibitors are rarely used compared with programmed death 1/programmed cell death ligand 1 inhibitors in esophageal cancer and other cancers, and the clinical benefit is unclear. We analyzed and summarized the efficacy and safety of cytotoxic T-lymphocyte-associated protein 4 immune checkpoint inhibitors in the treatment of esophageal cancer. Due to the lack of clinical applications, it is expected that cytotoxic T-lymphocyte-associated protein 4 immune checkpoint inhibitors in combination with other treatments may provide superior benefits and improve the prognosis of patients with esophageal cancer.