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利用单细胞转录组分析揭示EB病毒相关胃癌肿瘤微环境的差异

Differences in the Tumor Microenvironment of EBV-Associated Gastric Cancers Revealed Using Single-Cell Transcriptome Analysis.

作者信息

Salnikov Mikhail Y, Fonseca Gregory J, Mymryk Joe S

机构信息

Department of Microbiology and Immunology, Western University, London, ON N6A 3K7, Canada.

Meakins-Christie Laboratories, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada.

出版信息

Cancers (Basel). 2023 Jun 14;15(12):3178. doi: 10.3390/cancers15123178.


DOI:10.3390/cancers15123178
PMID:37370788
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10296402/
Abstract

Epstein-Barr virus (EBV) is a gamma-herpesvirus associated with nearly 10% of gastric cancers (GCs). These EBV-associated GCs (EBVaGCs) are molecularly, histopathologically, and clinically distinct from EBV-negative GCs (EBVnGCs). While viral genes in EBVaGCs contribute to the carcinogenesis process, viral proteins also represent foreign antigens that could trigger enhanced immune responses compared to EBVnGCs. Despite prior investigations of the EBVaGC tumor microenvironment (TME), the cellular composition has not been thoroughly explored. In this study, cellular subpopulations overrepresented in EBVaGCs were identified and molecularly characterized. Genes consistently expressed across both bulk tumor and single-cell RNA sequencing data were highlighted, with the expression across the identified cellular subpopulations analyzed. As expected, based on existing histopathological analysis, EBVaGC is characterized by abundant lymphocytic infiltration of the stroma. Our molecular analysis identified three unique immune cell subpopulations in EBVaGC: T and B cells expressing high levels of proliferation markers and B cells expressing T cell features. The proliferating T cell cluster also expressed markers of follicular T helper cells. Overall, EBVaGC also exhibited unique features indicative of a higher inflammatory response. These substantial differences within the TME suggest that further detailed exploration of the cellular composition of EBVaGCs is needed, which may identify cellular subpopulations and phenotypes associated with patient outcomes.

摘要

爱泼斯坦-巴尔病毒(EBV)是一种γ-疱疹病毒,与近10%的胃癌(GC)相关。这些与EBV相关的胃癌(EBVaGC)在分子、组织病理学和临床上与EBV阴性胃癌(EBVnGC)不同。虽然EBVaGC中的病毒基因有助于致癌过程,但病毒蛋白也代表外来抗原,与EBVnGC相比,可能引发更强的免疫反应。尽管之前对EBVaGC肿瘤微环境(TME)进行了研究,但细胞组成尚未得到充分探索。在本研究中,确定了在EBVaGC中过度表达的细胞亚群并对其进行了分子表征。强调了在批量肿瘤和单细胞RNA测序数据中一致表达的基因,并分析了在所确定的细胞亚群中的表达情况。正如预期的那样,基于现有的组织病理学分析,EBVaGC的特征是基质中有大量淋巴细胞浸润。我们的分子分析在EBVaGC中确定了三个独特的免疫细胞亚群:表达高水平增殖标志物的T细胞和B细胞以及表达T细胞特征的B细胞。增殖的T细胞簇还表达滤泡辅助性T细胞标志物。总体而言,EBVaGC还表现出表明更高炎症反应的独特特征。TME内的这些实质性差异表明,需要对EBVaGC的细胞组成进行进一步详细探索,这可能会确定与患者预后相关的细胞亚群和表型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/fae4f8cd2bfd/cancers-15-03178-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/9af27742a6a2/cancers-15-03178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/1699e5388df9/cancers-15-03178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/0abfe77ea416/cancers-15-03178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/c2a4f818885f/cancers-15-03178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/7306cb656173/cancers-15-03178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/fae4f8cd2bfd/cancers-15-03178-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/9af27742a6a2/cancers-15-03178-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/1699e5388df9/cancers-15-03178-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/0abfe77ea416/cancers-15-03178-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/c2a4f818885f/cancers-15-03178-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/7306cb656173/cancers-15-03178-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2baa/10296402/fae4f8cd2bfd/cancers-15-03178-g006.jpg

相似文献

[1]
Differences in the Tumor Microenvironment of EBV-Associated Gastric Cancers Revealed Using Single-Cell Transcriptome Analysis.

Cancers (Basel). 2023-6-14

[2]
Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion.

Viruses. 2023-1-7

[3]
The viral etiology of EBV-associated gastric cancers contributes to their unique pathology, clinical outcomes, treatment responses and immune landscape.

Front Immunol. 2024

[4]
Deregulation of immune response genes in patients with Epstein-Barr virus-associated gastric cancer and outcomes.

Gastroenterology. 2014-9-22

[5]
The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis.

Viruses. 2023-3-27

[6]
Expression of c-myc and PCNA in Epstein-Barr virus-associated gastric carcinoma.

Exp Ther Med. 2013-4

[7]
Prognostic Perspectives of STING and PD-L1 Expression and Correlation with the Prognosis of Epstein-Barr Virus-Associated Gastric Cancers.

Gut Liver. 2022-11-15

[8]
Differentiated tumor immune microenvironment of Epstein-Barr virus-associated and negative gastric cancer: implication in prognosis and immunotherapy.

Oncotarget. 2017-5-16

[9]
Tumor cell-expressed IL-15Rα drives antagonistic effects on the progression and immune control of gastric cancer and is epigenetically regulated in EBV-positive gastric cancer.

Cell Oncol (Dordr). 2020-12

[10]
Transcriptional analysis of immune genes in Epstein-Barr virus-associated gastric cancer and association with clinical outcomes.

Gastric Cancer. 2018-6-18

引用本文的文献

[1]
Viral oncogenesis in cancer: from mechanisms to therapeutics.

Signal Transduct Target Ther. 2025-5-12

[2]
Phosphoribosyl transferase domain containing 1: A prognostic biomarker in testicular germ cell tumors.

Mol Ther Oncol. 2025-2-28

[3]
Clinicopathological characteristics and prognosis of Epstein-Barr virus-associated gastric cancer.

Arch Virol. 2024-5-3

[4]
The viral etiology of EBV-associated gastric cancers contributes to their unique pathology, clinical outcomes, treatment responses and immune landscape.

Front Immunol. 2024

本文引用的文献

[1]
The EBV Gastric Cancer Resource (EBV-GCR): A Suite of Tools for Investigating EBV-Associated Human Gastric Carcinogenesis.

Viruses. 2023-3-27

[2]
Tumor-Infiltrating T Cells in EBV-Associated Gastric Carcinomas Exhibit High Levels of Multiple Markers of Activation, Effector Gene Expression, and Exhaustion.

Viruses. 2023-1-7

[3]
T follicular helper cells in cancer.

Trends Cancer. 2023-4

[4]
Parallel single-cell and bulk transcriptome analyses reveal key features of the gastric tumor microenvironment.

Genome Biol. 2022-12-22

[5]
CD160 Promotes NK Cell Functions by Upregulating Glucose Metabolism and Negatively Correlates With HIV Disease Progression.

Front Immunol. 2022

[6]
Treatment Advances in EBV Related Lymphoproliferative Diseases.

Front Oncol. 2022-4-19

[7]
EBV/HHV-6A dUTPases contribute to myalgic encephalomyelitis/chronic fatigue syndrome pathophysiology by enhancing TFH cell differentiation and extrafollicular activities.

JCI Insight. 2022-6-8

[8]
Molecular Basis of Epstein-Barr Virus Latency Establishment and Lytic Reactivation.

Viruses. 2021-11-23

[9]
T follicular helper cells: linking cancer immunotherapy and immune-related adverse events.

J Immunother Cancer. 2021-6

[10]
Characterization of Follicular Helper CD4 T Cells Using Multiplexed Imaging.

Front Immunol. 2021-2-3

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