Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF

Qi-Wei Zhang; Meng-Xuan Zhu; Wen-Feng Liu; Wei-Wei Rui; Yong Chen; Xiao-Yi Ding; Yong-Sheng Jiang; Zhi-Yuan Wu; Bin-Bin Liu

doi:10.1016/j.tranon.2024.101954

Identification of clinically relevant subsets CD39⁺PD-1⁺CD8⁺ T cells and CD39⁺ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF

Transl Oncol. 2024 Jun:44:101954. doi: 10.1016/j.tranon.2024.101954. Epub 2024 Apr 11.

Authors

Qi-Wei Zhang¹, Meng-Xuan Zhu², Wen-Feng Liu³, Wei-Wei Rui⁴, Yong Chen⁵, Xiao-Yi Ding⁶, Yong-Sheng Jiang⁷, Zhi-Yuan Wu⁸, Bin-Bin Liu⁹

Affiliations

¹ Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.
² Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
³ Department of Gastroenterology and Hepatology, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 180 Fenglin Road, Shanghai 200032, China.
⁴ Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁵ Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁶ Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China. Electronic address: dxy10456@rjh.com.cn.
⁷ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China; Research Institute of Pancreatic Diseases, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: jys01h32@rjh.com.cn.
⁸ Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China. Electronic address: wzy11549@rjh.com.cn.
⁹ Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 180 Fenglin Road, Shanghai 200032, China. Electronic address: liu.binbin@zs-hospital.sh.cn.

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is an aggressive liver malignancy with limited treatment options and a dismal prognosis. The tumor immune microenvironment (TIME) is crucial for iCCA progression, yet its comprehensive characterization remains incomplete. This study utilized mass cytometry by time of flight (CyTOF) to comprehensively analyze immune cell populations in fresh iCCA tumor samples and adjacent peritumor liver tissues. Notably, NK cell percentages significantly decreased in iCCA lesions compared to peritumor liver tissues. Conversely, an enrichment of immunosuppressive CD39⁺Foxp3⁺CD4⁺ regulatory T cells (CD39⁺T-regs) and exhausted-like CD8⁺T cells (with pronounced CD39 and PD-1 expression) within TIME was identified and confirmed by multiplex immunofluorescence staining in an independent patient cohort (n = 140). Crucially, tumor-infiltrating CD39⁺T-regs and CD39⁺PD-1⁺CD8⁺T cells emerged as independent prognostic indicators associated with an unfavorable prognosis in iCCA. These findings unveil the intricate immune landscape within iCCA, offering valuable insights for disease management and novel cancer immunotherapies.

Keywords: Immune microenvironment; Intrahepatic cholangiocarcinoma; Mass cytometry; Single cell analysis.