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Cancers 2019, 11(4), 541; https://doi.org/10.3390/cancers11040541

Low CD8+ T Cell Infiltration and High PD-L1 Expression Are Associated with Level of CD44+/CD133+ Cancer Stem Cells and Predict an Unfavorable Prognosis in Pancreatic Cancer

1
Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
2
Department of Clinical Medical Research, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
3
Division of General Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 704, Taiwan
*
Author to whom correspondence should be addressed.
Received: 1 March 2019 / Revised: 8 April 2019 / Accepted: 12 April 2019 / Published: 15 April 2019
(This article belongs to the Special Issue Advances in Cancer Stem Cell Research)
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Abstract

Cancer immunotherapy targeting immune checkpoints has exhibited promising clinical outcomes in many cancers, but it offers only limited benefits for pancreatic cancer (PC). Cancer stem cells (CSCs), a minor subpopulation of cancer cells, play important roles in tumor initiation, progression, and drug resistance. Accumulating evidence suggests that CSCs employ immunosuppressive effects to evade immune system recognition. However, the clinical implications of the associations among CD8+ T cells infiltration, programmed death receptor ligand-1 (PD-L1) expression, and CSCs existence are poorly understood in PC. Immunostaining and quantitative analysis were performed to assess CD8+ T cells infiltration, PD-L1 expression, and their relationship with CD44+/CD133+ CSCs and disease progression in PC. CD8+ T cells infiltration was associated with better survival while PD-L1 expression was correlated with PC recurrence. Both the low CD8+ T cells infiltration/high PD-L1 expression group and the high CD8+ T cells infiltration/high PD-L1 expression group show high levels of CD44+/CD133+ CSCs, but patients with low CD8+ T cells infiltration/high PD-L1 expression had worse survival and higher recurrence risk than those with high CD8+ T cells infiltration/high PD-L1 expression. Moreover, high infiltration of CD8+ T cells could reduce unfavorable prognostic effect of high co-expression of PD-L1 and CD44/CD133. Our study highlights an interaction among CD8+ T cells infiltration, PD-L1 expression, and CD44+/CD133+ CSCs existence, which contributes to PC progression and immune evasion. View Full-Text
Keywords: pancreatic cancer; T cells; cancer stem cells; CD8; PD-L1; CD44; CD133; immunotherapy pancreatic cancer; T cells; cancer stem cells; CD8; PD-L1; CD44; CD133; immunotherapy
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Hou, Y.-C.; Chao, Y.-J.; Hsieh, M.-H.; Tung, H.-L.; Wang, H.-C.; Shan, Y.-S. Low CD8+ T Cell Infiltration and High PD-L1 Expression Are Associated with Level of CD44+/CD133+ Cancer Stem Cells and Predict an Unfavorable Prognosis in Pancreatic Cancer. Cancers 2019, 11, 541.

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