Characterization Of Stemness And Immunogenicity Of Cancer Stem Cells Of Intrahepatic Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is one of leading causes of cancer related mortality with limited treatment options. Cancer stem cells (CSCs) have been recognized as a critical driving force of CCA initiation and drug-resistance, representing an attractive and innovative therapeutic target. In this study, single-cell transcriptomic landscape of cancer biospecimens from 10 patients with intrahepatic cholangiocarcinoma (iCCA) were investigated. We characterized CSC in CCA subtypes and identified the differential genes between CSCs and malignant cells. We found that there is the heterogeneity of CSCs in iCCA in terms of stemness makers and immunity per se. Our study pointed to low immunity spectrum of CSCs of iCCA that contribute to immune evasion. We found that SPP1 gene is highly expressed compared to malignant cells in CSC, which indicated that Osteopontin, which is coded by SPP1, may acts as an immune checkpoint to suppress T cell activation and confer host tumor immune tolerance. Our analysis from TCGA database also confirmed that, stemness was strongly associated with cell native immunosuppressive pathway and SPP1 gene expression. Our data indicate that CSC evade innate immune suppression through induced SPP1 expression and Osteopontin may serve as a potential therapeutic intervention for CCA patients. Citation Format: Jianyang Fu, Yunhua Zhu, Nichole A. McGrath, Maggie Cam, Changqing Xie. Characterization of stemness and immunogenicity of cancer stem cells of intrahepatic cholangiocarcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-037.