Immune Related Pathological Features and Predictive Score in Intrahepatic Cholangiocarcinoma Treated With Combined Conversion Immunotherapy.

Résumé

Immune checkpoint inhibitor (ICI)-based combined neoadjuvant/conversion therapy (NAT) is increasingly utilized in the management of initially unresectable intrahepatic cholangiocarcinoma (iCCA). Reliable biomarkers in predicting treatment and survival outcome remain underdeveloped. Here we assessed immune-related pathological features (irPF) in pre-treatment biopsy specimens of initially unresectable iCCA treated by ICI-based conversion therapy. A predictive scoring system (immune therapy predictive score, iTPS) was developed to predict the patients' oncological outcome. We evaluated 13 irPF (tumor infiltrating lymphocyte, mature tertiary lymphoid structure, lymphoid aggregate, dense plasma cell infiltration, granuloma, neutrophil, foamy macrophage, necrosis, cholesterol cleft, hemosiderin deposition, giant cell formation, neovascularization and mature fibrosis) in hematoxylin-eosin (HE) stained biopsy specimen slides from 95 iCCA patients. Cox regression analysis was used to evalutate the correlation between these features and recurrence-free survival (RFS) and overall survival (OS). Features showing correlation with survival were selected for iTPS to develop a binary iTPS scheme. Four features (immature fibrosis, tumor-infiltrating lymphocytes, lymphoid aggregate and hemosiderin) were included in iTPS. A binary iTPS scheme showed patients with low iTPS displaying significantly better RFS (hazard ratio [HR]: 1.83; 95% confidence interval [CI]: 1.02∼3.27, P = 0.04) and OS (HR: 12.9; CI: 3.07∼54.18, P < 0.001). In conclusion, we developed an iTPS scheme based on routine HE-stained pretreatment biopsy slides. The iTPS can predict the RFS and OS of iCCA patients treated by combined ICI-based conversion therapy. iTPS is a good candidate predictive biomarker in iCCA and provides a new perspective in understanding the tumor immune microenvironment in immunotherapy.