Acquired Resistance Mechanisms to PD-L1 Blockade in a Patient With Microsatellite Instability-High Extrahepatic Cholangiocarcinoma

摘要

Introduction: Cholangiocarcinoma (CCA) is an aggressive disease, with poor prognosis and limited therapeutic options. Standard chemotherapy (ChT) for advanced CCA is still unsatisfactory, with a median overall survival of < 12 months. CCA is a molecularly heterogeneous disease, and several potential molecular targets are reported in up to 47% of patients Among these, microsatellite instability-high (MSI-H) status is found in < 1% of cases, but it is relevant given the unprecedented benefit of MSI-H cancers from immune checkpoint inhibitors. However, mechanisms of acquired resistance to immune checkpoint inhibition in MSI-H patients need to be elucidated. Here, we present the clinical history and molecular characterization of a patient with advanced, MSI-H distal CCA (dCCA) treated with ChT, immunotherapy (10), and repeated surgeries and longitudinally profiled in both tumor samples and liquid biopsies.