J.Jpn. Surg. Soc.. 127(2): 192-197, 2026

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Feature topic

IMMUNE CHECKPOINT INHIBITOR THERAPY FOR BILIARY AND PANCREATIC CANCERS

Improving outcomes for biliary and pancreatic cancers, both of which have extremely poor prognoses, remains an urgent challenge. Immune checkpoint inhibitors (ICIs), initially approved for malignant melanoma, non-small cell lung cancer, and renal cell carcinoma, have since become standard treatments for gastric and hepatocellular cancers. In 2022, the TOPAZ-1 trial was conducted for unresectable biliary tract cancer, revealing that adding the PD-L1 inhibitor durvalumab to gemcitabine plus cisplatin (GC therapy) led to longer overall survival compared with standard GC therapy alone (12.8 vs 11.5 months). Furthermore, in 2023, the addition of the PD-1 inhibitor pembrolizumab to GC therapy also demonstrated improved overall survival over GC therapy alone (12.7 vs 10.9 months). Consequently, the combination of ICIs with GC therapy is now recommended as the standard of care for unresectable biliary tract cancer, as reflected in the revised 4th edition of the clinical guidelines. Conversely, the efficacy of ICIs as monotherapy for pancreatic cancer has not been established. Pembrolizumab is effective only in MSI-H or tumor mutational burden-high pancreatic cancers. The limited efficacy in pancreatic cancer is attributed to its “cold tumor” microenvironment, characterized by low immunogenicity and a dense stroma that acts as a physical barrier. Current research is focused on converting “cold tumors” into “hot tumors” through combinations with chemotherapy, radiotherapy, and molecular-targeted therapies.

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