Immunotherapy as a treatment for biliary tract cancers: A review of approaches with an eye to the future

Biliary tract cancers (BTC) are aggressive malignancies associated with resistance to chemotherapy and poor prognostic rates. Therefore, novel treatment approaches are in need. Immunotherapy represents a promising breakthrough that uses a patient's immune system to target a tumor. This treatment approach has shown immense progress with positive results for selected cancers such as melanoma and nonsmall cell lung cancer. Initial preclinical data and preliminary clinical studies suggest encouraging mechanistic effects for immunotherapy in BTC offering the hope for an expanding therapeutic role for this disease. These approaches include targeted tumor antigen therapy via peptide and dendritic cell-based vaccines, allogenic cell adoptive immunotherapy, and the use of inhibitory agents targeting the immune checkpoint receptor pathway and multiple components of the tumor microenvironment. At this time demonstrating efficacy in larger clinical trials remains imperative. A multitude of ongoing trials aim to successfully translate mechanistic effects into antitumor efficacy and ultimately aim to incorporate immunotherapy into the routine management of BTC. With further research efforts, the optimization of dosing and therapeutic regimens, the identification of novel tumor antigens and a better understanding of alternative checkpoint pathway receptor expression may provide additional targets for rational combinatorial therapies which enhance the effects of immunotherapy and may offer hope for further advancing treatment options. Ultimately, the challenge remains to prospectively identify the subsets of patients with BTC who may respond to immunotherapy, and devising alternative strategies to sensitize those that do not with the hopes of improving outcomes for all with this deadly disease.