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

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 t...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2024-06-01
Series:Translational Oncology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1936523324000810
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author 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
author_facet 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
author_sort Qi-Wei Zhang
collection DOAJ
description 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.
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spelling doaj.art-de5c5f66fd054f6e8ec00f9b6abf70c42024-04-13T04:21:11ZengElsevierTranslational Oncology1936-52332024-06-0144101954Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOFQi-Wei Zhang0Meng-Xuan Zhu1Wen-Feng Liu2Wei-Wei Rui3Yong Chen4Xiao-Yi Ding5Yong-Sheng Jiang6Zhi-Yuan Wu7Bin-Bin Liu8Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, ChinaDepartment of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment 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, ChinaDepartment of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, ChinaDepartment of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China; Corresponding authors at: Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.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; Corresponding author at: Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China; Corresponding authors at: Department of Interventional Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197, Ruijin Er Road, Shanghai 200025, China.Liver Cancer Institute, Zhongshan Hospital, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Fudan University, 180 Fenglin Road, Shanghai 200032, ChinaIntrahepatic 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.http://www.sciencedirect.com/science/article/pii/S1936523324000810Mass cytometrySingle cell analysisIntrahepatic cholangiocarcinomaImmune microenvironment
spellingShingle 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
Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF
Translational Oncology
Mass cytometry
Single cell analysis
Intrahepatic cholangiocarcinoma
Immune microenvironment
title Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF
title_full Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF
title_fullStr Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF
title_full_unstemmed Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF
title_short Identification of clinically relevant subsets CD39+PD-1+CD8+ T cells and CD39+ regulatory T cells in intrahepatic cholangiocarcinoma using single-cell CyTOF
title_sort identification of clinically relevant subsets cd39 pd 1 cd8 t cells and cd39 regulatory t cells in intrahepatic cholangiocarcinoma using single cell cytof
topic Mass cytometry
Single cell analysis
Intrahepatic cholangiocarcinoma
Immune microenvironment
url http://www.sciencedirect.com/science/article/pii/S1936523324000810
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