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V结构域免疫球蛋白T细胞激活抑制因子的高密度浸润上调人胰腺癌中的免疫细胞

High-Density Infiltration of V-domain Immunoglobulin Suppressor of T-cell Activation Up-regulated Immune Cells in Human Pancreatic Cancer.

作者信息

Liu Jinʼe, Xie Xiaoxue, Xuan Chunxiao, Li Tingting, Wang Lanlan, Teng Lianghong, Liu Jun

机构信息

Department of Pathology, Xuanwu Hospital, Beijing, China.

出版信息

Pancreas. 2018 Jul;47(6):725-731. doi: 10.1097/MPA.0000000000001059.


DOI:10.1097/MPA.0000000000001059
PMID:29771768
Abstract

UNLABELLED: V-domain immunoglobulin suppressor of T-cell activation (VISTA) is constitutively expressed in hematopoietic lineage and is highly up-regulated in tumor infiltrated myeloid cells and regulatory T-cells in animal models. However, its expression in human pancreatic tumor microenvironment remains unknown. In this research, we aimed at the expression of VISTA in human pancreatic cancer samples. METHODS: We performed immunohistochemistry to determine VISTA expression in human pancreatic cancer samples. RESULTS: We found that 88.46% of the patients showed high-density infiltration of polymorphonuclear neutrophils and mononuclear immune cells with up-regulated expression of VISTA in cancer tissues, especially in the necrotic foci. Interestingly, it was minimally expressed in pancreatic cancerous cells and was not detectable in either normal ducts or islet cells in cancerous or normal pancreatic tissues. CONCLUSIONS: We conclude that VISTA is predominantly expressed and up-regulated in the high-density infiltrated immune cells but minimal in human pancreatic cancerous cells. Our results for the first time highlight pancreatic immunosuppressive tumor microenvironment contributed by VISTA and its potential as a prominent target for pancreatic cancer immunotherapy.

摘要

未标记:T细胞活化的V结构域免疫球蛋白抑制因子(VISTA)在造血谱系中组成性表达,在动物模型的肿瘤浸润髓样细胞和调节性T细胞中高度上调。然而,其在人胰腺肿瘤微环境中的表达仍不清楚。在本研究中,我们旨在研究VISTA在人胰腺癌样本中的表达。 方法:我们进行免疫组织化学以确定VISTA在人胰腺癌样本中的表达。 结果:我们发现88.46%的患者癌组织中多形核中性粒细胞和单核免疫细胞呈高密度浸润,VISTA表达上调,尤其是在坏死灶中。有趣的是,它在胰腺癌细胞中表达极少,在癌性或正常胰腺组织的正常导管或胰岛细胞中均未检测到。 结论:我们得出结论,VISTA主要在高密度浸润的免疫细胞中表达并上调,但在人胰腺癌细胞中表达极少。我们的结果首次突出了VISTA促成的胰腺免疫抑制肿瘤微环境及其作为胰腺癌免疫治疗突出靶点的潜力。

相似文献

[1]
High-Density Infiltration of V-domain Immunoglobulin Suppressor of T-cell Activation Up-regulated Immune Cells in Human Pancreatic Cancer.

Pancreas. 2018-7

[2]
Comparison of immune infiltrates in melanoma and pancreatic cancer highlights VISTA as a potential target in pancreatic cancer.

Proc Natl Acad Sci U S A. 2019-1-11

[3]
The Expression Pattern and Clinical Significance of the Immune Checkpoint Regulator VISTA in Human Breast Cancer.

Front Immunol. 2020

[4]
VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy.

Trends Immunol. 2021-3

[5]
VISTA expressed in tumour cells regulates T cell function.

Br J Cancer. 2018-11-9

[6]
Investigation of the effects of the toll-like receptor 4 pathway on immune checkpoint vista in pancreatic cancer.

Invest New Drugs. 2022-6

[7]
The Role of V-Domain Ig Suppressor of T Cell Activation (VISTA) in Cancer Therapy: Lessons Learned and the Road Ahead.

Front Immunol. 2021

[8]
Differential contribution of three immune checkpoint (VISTA, CTLA-4, PD-1) pathways to antitumor responses against squamous cell carcinoma.

Oral Oncol. 2016-6

[9]
Synergistic anti-pancreatic cancer immunological effects by treatment with reduced expression in immortalized cells/dickkopf-3 protein and peripheral blood mononuclear cells.

J Gastroenterol Hepatol. 2016-6

[10]
Expression and function of VISTA on myeloid cells.

Biochem Pharmacol. 2024-4

引用本文的文献

[1]
Pan-cancer analysis of co-inhibitory molecules revealing their potential prognostic and clinical values in immunotherapy.

Front Immunol. 2025-3-24

[2]
A pair of promising immune checkpoints PSGL-1 and VISTA from immunotolerance to immunotherapy.

Biomark Res. 2024-12-2

[3]
VISTA-mediated immune evasion in cancer.

Exp Mol Med. 2024-11

[4]
PD-1H/VISTA mediates immune evasion in acute myeloid leukemia.

J Clin Invest. 2024-2-1

[5]
Clinical and research updates on the VISTA immune checkpoint: immuno-oncology themes and highlights.

Front Oncol. 2023-9-15

[6]
High VISTA expression is linked to a potent epithelial-mesenchymal transition and is positively correlated with PD1 in breast cancer.

Front Oncol. 2023-4-20

[7]
VISTA expression and patient selection for immune-based anticancer therapy.

Front Immunol. 2023

[8]
B7 Family Members in Pancreatic Ductal Adenocarcinoma: Attractive Targets for Cancer Immunotherapy.

Int J Mol Sci. 2022-11-30

[9]
Tumor Budding Is an Independent Prognostic Factor in Pancreatic Adenocarcinoma and It Positively Correlates with PD-L1 Expression on Tumor Cells.

Biomedicines. 2022-7-21

[10]
Discovery of Novel Inhibitors From Medicinal Plants for V-Domain Ig Suppressor of T-Cell Activation.

Front Mol Biosci. 2021-10-26

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