Abstract:Immunotherapy provides a new treatment option for biliary tract cancers (BTC), especially for patients with advanced stages. Durvalumab, with its acceptable drug toxicity and significant improvement in prognosis, has emerged as a first-line treatment for advanced BTC. However, it should not be overlooked that while immunotherapy benefits BTC patients, it also faces two challenges: treatment resistance and hyperprogression. Both of these challenges have a relatively high incidence, impacting the efficacy of immunotherapy and potentially accelerating tumor progression. Here, the authors outline the immune-related biological processes involved by delving into the mechanisms underlying these two challenges to lay a foundation for developing regimens to tackle immunotherapy resistance and hyperprogression, to enhance the efficacy of immune therapy for BTC and refine the comprehensive strategy for surgical treatment of biliary tract conditions.