Immunotherapy in biliary tract cancer: effective but not enough?

Biliary tract cancer (BTC) is an aggressive cancer arising from biliary epithelial cells. The combination of immune checkpoint inhibitors (ICIs) with other anticancer therapies has recently emerged as a new approach for BTC, and combinatorial strategies including chemotherapy plus immunotherapy are the current first-line standard in the metastatic setting. However, these combinations are effective only for a niche of patients and long-term responses are rare.

This review will focus on available data and ongoing clinical trials aimed at addressing the resistance mechanisms in BTC patients receiving ICIs that frequently experience primary resistance or short-term responses.

The integration of immunotherapy with chemotherapy has established itself as a new standard treatment, while innovative approaches including dual immunotherapy, pairing ICIs with targeted therapies and combining ICIs with locoregional therapies have shown encouraging synergy. Nonetheless, issues like primary and secondary resistance, the immunosuppressive TME of BTC, and the lack of reliable biomarkers of response remain major challenges.