Immunotherapy in cholangiocarcinoma: From concept to clinical trials

Abstract

Cholangiocarcinoma (CCA) is an epithelial malignancy of the bile tract that has a poor prognosis and lacks effective treatments. The first-line systemic therapy for CCA patients is gemcitabine combined with cisplatin, and the efficacy and safety of immunotherapies are still unclear. The special tumor microenvironment (TME) of CCA, which results in a T cell exclusion mechanism, suppresses the antitumor immune response and promotes tumorigenesis. Immunotherapies aim to reestablish the TME of the CCA and remove obstacles against antitumor immunity. Immune checkpoint inhibitors (ICIs), chimeric antigen receptor (CAR) T-cells, and tumor vaccines are the main immunotherapies practiced at present. Some clinical trials of these agents have obtained effective responses, while some have not. The identification of reliable predictive biomarkers for immunotherapy is urgently needed to obtain better responses in CCA. In this article, we elucidate the concept of T cell exclusion and discuss the current evidence from clinical trials for immunotherapies.

Keywords

• Cholangiocarcinoma
• immunotherapy
• tumor microenvironment
• immune checkpoint inhibitors