Cancer stem cell marker-positive tumour nests in intrahepatic cholangiocarcinoma are related to epithelial type CD1a-positive dendritic cell infiltration and to high Sox9 expression
Background It is yet a mystery whether dendritic cells (DCs) contact cancer stem cells (CSCs) and uptake CSC antigens in intrahepatic cholangiocarcinoma (ICC). The aim of this study was to examine the histological relationship between tumour cells expressing CSC markers and DCs infiltrating ICC. In addition, clinicopathological factors, including progression-free survival (PFS) and overall survival (OS), were compared between cases with many and few CSC marker-positive cells. Materials and
... Materials and methods Resected tissue sections of 22 cases with ICC were used for immunostaining to detect DC infiltration into ICC tumour nests positive for CD1a, DC-SIGN, DEC205, DC-LAMP, and CD123 and to detect ICC tumour cells positive for CSC markers such as CD44v9, EpCAM, and Sox9. The relationship between the number of CSC marker-positive cells and ICC clinicopathological factors was examined by Kaplan-Meier method and univariate and multivariate analyses using the Cox proportional hazards model. Results CD1a+ immature DCs infiltrated ICC tumour nests significantly more than the other types of DCs. Furthermore, they were frequently localized within CD44v9− and EpCAMhigh ICC tumour nests. According to Kaplan-Meier method, PFS and OS were longer in the Sox9high group than in the Sox9low group, and according to both univariate and multivariate analyses, Sox9 expression was an independent factor. Conclusion The present study first demonstrated that CD1a+ immature DCs frequently infiltrated CD44v9− and EpCAMhigh ICC tumour nests, suggesting the possibility of cell-to-cell contact between epithelial type immature DCs and CSCs in ICC. Furthermore, it was suggested that Sox9 expression in ICC may be a prognostic factor.