Characterization of Immunogenicity of Malignant Cells with Stemness in Intrahepatic Cholangiocarcinoma by Single-Cell RNA Sequencing

Jing Bian; Jianyang Fu; Xin Wang; Jihye Lee; Gagandeep Brar; Freddy E Escorcia; Maggie Cam; Changqing Xie

doi:10.1155/2022/3558200

Characterization of Immunogenicity of Malignant Cells with Stemness in Intrahepatic Cholangiocarcinoma by Single-Cell RNA Sequencing

Stem Cells Int. 2022 Apr 29:2022:3558200. doi: 10.1155/2022/3558200. eCollection 2022.

Authors

Jing Bian¹, Jianyang Fu², Xin Wang², Jihye Lee², Gagandeep Brar³, Freddy E Escorcia^{4

5}, Maggie Cam¹, Changqing Xie^{2

5}

Affiliations

¹ CCR Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
² Gastrointestinal Malignancies Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
³ Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, New York, USA.
⁴ Molecular Imaging Branch, Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
⁵ NCI CCR Liver Cancer Program, USA.

Abstract

Cancer stem cells (CSCs) are responsible for long-term maintenance of tumors and thought to play a role in treatment resistance. The interaction between stemness and immunogenicity of CSCs in the intrahepatic cholangiocarcinoma (iCCA) is largely unknown. Here, we used single-cell transcriptomic data to study immunogenicity of malignant cells in human iCCA. Using an established computerized method CytoTRACE, we found significant heterogeneity in stemness/differentiation states among malignant cells. We demonstrated that the high stemness malignant cells express much lower levels of major histocompatibility complex II molecules when compared to low stemness malignant cells, suggesting a role of immune evasion in high stemness malignant cells. In addition, high stemness malignant iCCA cells exhibited significant expression of certain cytokine members, including CCL2, CCL20, CXCL1, CXCL2, CXCL6, CXCL8, TNFRSF12A, and IL6ST, indicating communication with surrounding immune cells. These results indicate that high stemness malignant cells retain their intrinsic immunological feature that facilitate the escape of immune surveillance.