Immunotherapy of cholangiocarcinoma: Therapeutic strategies and predictive biomarkers

Cholangiocarcinoma (CCA) is a group of malignant heterogeneous cancer arising from the biliary tree. CCA has become a global health problem with rising incidence and mortality that threatens the health of human beings. The immune microenvironment of CCA is characterized by abundant cancer-associated fibroblast and suppressive immune components. The increasing body of knowledge and recent developments in transcriptomic studies have given insight into the immune landscape of CCA, paving the way for better application of immunotherapy. Immunotherapy mainly applies in a limited subset of CCA with deficient mismatch and high microsatellite instability. With limited response rates and treatment efficacy, researchers are looking into novel strategies on combination strategies and alternatives, such as immune vaccines and adoptive cell therapy. Biomarker identification is also critical for patient selection. We present an up-to-date summary of the current research on immunotherapy for CCA patients, covering pre-clinical and clinical exploration beyond immune checkpoint inhibitors, immune vaccines, and adoptive cell therapy. In addition, we review the promising biomarkers for CCA immunotherapy and discuss recent development.