Abstract
Biliary tract cancer (BTC) is a rare and aggressive type of malignancy characterized by heterogeneity both in tumor biology and in the immune microenvironment. Most patients are diagnosed with advanced-stage disease and have limited curative options. Although the introduction of immune-checkpoint inhibitors (ICI) has transformed the treatment landscape for several solid tumors, their effects on BTC remain modest. New combinations have promoted incremental improvements in the survival of patients with advanced BTC, but the complex interplay between immune therapies and the tumor microenvironment continues to be a major challenge to improve therapeutic outcomes. Nonetheless, ongoing studies are investigating combinations that may potentially improve results in this lethal disease. This review provides an overview of the evolving role of ICIs in BTC, discusses the impact of tumor heterogeneity on treatment response, and explores future directions to optimize patient selection.