scholarly journals Efficacy of Immune Checkpoint Inhibitors in Metastatic Epstein-Barr Virus Associated Gastric Cancer (EBVaGC): A Case Series and Review of Literature

2021 ◽  
Author(s):  
Shimeng Liang ◽  
Weibing Leng ◽  
Dan Jiang ◽  
Ming Liu ◽  
Dan Cao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Immune Checkpoint Inhibitors ◽  
Epstein Barr Virus ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Metastatic Gastric Cancer ◽  
Pooled Analysis ◽  
Barr Virus ◽  
Epstein Barr

Abstract Background Immunotherapy has revolutionized the treatment of malignant tumors. However, limited clinical data are available to report the efficacy of immune checkpoint inhibitors (ICIs) on Epstein-Barr virus-associated gastric carcinoma. Methods In this study, we report a case series of five patients with metastatic Epstein-Barr virus-associated gastric carcinoma who were treated with ICIs and to perform a pooled analysis of published cases to investigate the efficacy of ICIs in Epstein-Barr virus-associated gastric carcinoma patients. Results Between 2018 and 2020, five metastatic gastric cancer patients with EBV positivity who received PD-1 antibodies treatment were included in the analysis at the authors’ institution. Furthermore, we performed a pooled analysis of the contemporary literature. In our case series, two patients experienced partial response (PR); one patient achieved complete response (CR), whereas two patients had progression disease (PD), resulting an ORR of 60%. In the pooled analysis of all 36 patients, ORR was 48.6% (17/35). For the first line and later lines, it was 75% (3/4) and 45.2% (14/31) respectively. The ORR was 46.7% (14/30) for ICIs monotherapy and improved to 60% (3/5) by combination with chemotherapy. Conclusions These results demonstrated that an EBV-positive status was a reliable biomarker for immunotherapy in metastatic gastric cancer, especially for monotherapy. Immunotherapy combined with chemotherapy may be a better strategy, warranting further large-scale clinical trials for validation.

scholarly journals Establishment of a Screening Method for Epstein-Barr Virus-Associated Gastric Carcinoma by Droplet Digital PCR

2019 ◽  
Vol 7 (12) ◽  
pp. 628 ◽  
Author(s):  
Takuya Shuto ◽  
Jun Nishikawa ◽  
Kanami Shimokuri ◽  
Ayaka Yanagi ◽  
Tatsuya Takagi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
Screening Method ◽  
Complete Agreement ◽  
Quantitative Detection ◽  
Serum Samples ◽  
Barr Virus ◽  
Ebv Dna ◽  
Epstein Barr

Background: Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is classified as one of the molecular subtypes of gastric cancer. We used droplet digital polymerase chain reaction (ddPCR) to enable highly sensitive and quantitative detection of EBV. Methods: EBV-DNA load was calculated based on the copy number of the BamH1-W fragment of EBV by ddPCR, and the cut-off value of EBV-DNA load was set. We conducted both ddPCR and EBER1 ISH to examine whether their results coincided in 158 gastric cancer specimens of unknown EBV status. We prepared 26 biopsy specimens and 49 serum samples including EBVaGC and assayed them by ddPCR. Results: The median values of EBV-DNA load for EBVaGC and EBV-negative control were 17.0 and 0.00308, respectively. A cut-off value of 0.032 was determined for which the sensitivity was 1. Among the 158 gastric cancer specimens, 14 lesions were judged as EBV-positive by the 0.032 cut-off value determined by ddPCR. The results of ddPCR and EBER1 ISH were in complete agreement. Even when using a biopsy specimen as a sample for ddPCR, the EBV-DNA load of all EBVaGCs was larger than the cut-off value. Conclusions: We established a new method of diagnosing EBVaGC from tissue samples by ddPCR.

scholarly journals Epstein-Barr Virus miR-BART17-5p Promotes Migration and Anchorage-Independent Growth by Targeting Kruppel-Like Factor 2 in Gastric Cancer

2020 ◽  
Vol 8 (2) ◽  
pp. 258 ◽  
Author(s):  
Jae Hee Yoon ◽  
Kyoungmi Min ◽  
Suk Kyeong Lee
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
The Cancer Genome Atlas ◽  
Sequencing Data ◽  
Ags Cells ◽  
Anchorage Independent Growth ◽  
Barr Virus ◽  
Epstein Barr ◽  
Bart Mirnas

Epstein-Barr virus (EBV) infects more than 90% of the global population and is associated with a variety of tumors including nasopharyngeal carcinoma, Hodgkin lymphoma, natural killer/T lymphoma, and gastric carcinoma. In EBV-associated gastric cancer (EBVaGC), highly expressed EBV BamHI A rightward transcripts (BART) miRNAs may contribute to tumorigenesis with limited viral antigens. Despite previous studies on the targets of BART miRNAs, the functions of all 44 BART miRNAs have not been fully clarified. Here, we used RNA sequencing data from the Cancer Genome Atlas to find genes with decreased expression in EBVaGC. Furthermore, we used AGS cells infected with EBV to determine whether expression was reduced by BART miRNA. We showed that the expression of Kruppel-like factor 2 (KLF2) is lower in AGS-EBV cells than in the AGS control. Using bioinformatics analysis, four BART miRNAs were selected to check whether they suppress KLF2 expression. We found that only miR-BART17-5p directly down-regulated KLF2 and promoted gastric carcinoma cell migration and anchorage-independent growth. Our data suggest that KLF2 functions as a tumor suppressor in EBVaGC and that miR-BART17-5p may be a valuable target for effective EBVaGC treatment.

scholarly journals Exosomes of Epstein-Barr Virus-Associated Gastric Carcinoma Suppress Dendritic Cell Maturation

2020 ◽  
Vol 8 (11) ◽  
pp. 1776
Author(s):  
Munetoshi Hinata ◽  
Akiko Kunita ◽  
Hiroyuki Abe ◽  
Yasuyuki Morishita ◽  
Kei Sakuma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dendritic Cell ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
Gastric Cancer Cell ◽  
Dendritic Cell Maturation ◽  
Cell Maturation ◽  
Barr Virus ◽  
Gastric Cancer Cell Lines ◽  
Epstein Barr

The Epstein-Barr virus (EBV)-associated gastric carcinoma (EBVaGC) is characterized by the infiltration of lymphocytes and a unique tumor microenvironment. Exosomes from cancer cells are essential for intercellular communication. The aims of this study were to investigate the secretion of EBVaGC exosomes and their physiological effect on dendritic cell maturation in vitro and to characterize dendritic cells (DCs) in EBVaGC in vivo. Western blotting analysis of CD63 and CD81 of exosomes from EBV-infected gastric cancer cell lines indicated an increase in exosome secretion. The fraction of monocyte-derived DCs positive for the maturation marker CD86 was significantly suppressed when incubated with exosomes from EBV-infected gastric cancer cell lines. Immunohistochemical analysis of GC tissues expressing DC markers (S100, Langerin, CD1a, CD83, CD86, and BDCA-2) indicated that the density of DCs was generally higher in EBVaGC than in EBV-negative GC, although the numbers of CD83- and CD86-positive DCs were decreased in the group with high numbers of CD1a-positive DCs. A low number of CD83-positive DCs was marginally correlated with worse prognosis of EBVaGC in patients. EBVaGC is a tumor with abundant DCs, including immature and mature DCs. Moreover, the maturation of DCs is suppressed by exosomes from EBV-infected epithelial cells.

scholarly journals Improved survival of gastric cancer with tumour Epstein–Barr virus positivity: an international pooled analysis

Gut ◽  
2013 ◽  
Vol 63 (2) ◽  
pp. 236-243 ◽  
Author(s):  
M Constanza Camargo ◽  
Woo-Ho Kim ◽  
Anna Maria Chiaravalli ◽  
Kyoung-Mee Kim ◽  
Alejandro H Corvalan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epstein Barr Virus ◽  
Pooled Analysis ◽  
Barr Virus ◽  
Epstein Barr

Mo1587 Epstein-Barr Virus Positivity as a Prognostic Indicator in Gastric Cancer: an International Pooled Analysis

2012 ◽  
Vol 142 (5) ◽  
pp. S-635
Author(s):  
M. Constanza Camargo ◽  
Woo Ho Kim ◽  
Anna Maria Chiaravalli ◽  
Kyoung-Mee Kim ◽  
Alejandro H. Corvalan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epstein Barr Virus ◽  
Prognostic Indicator ◽  
Pooled Analysis ◽  
Barr Virus ◽  
Epstein Barr

scholarly journals Comprehensive Multi-Omics Analysis Reveals Aberrant Metabolism of Epstein–Barr-Virus-Associated Gastric Carcinoma

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1220 ◽  
Author(s):  
Yoon ◽  
Kim ◽  
Long ◽  
Min ◽  
Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Gastric Carcinoma ◽  
Epstein Barr Virus ◽  
Tissue Samples ◽  
Barr Virus ◽  
Advanced Gastric Carcinoma ◽  
Metabolic Genes ◽  
Epithelial Cell Lines ◽  
Epstein Barr ◽  
Gastric Cancer Patients

The metabolic landscape of Epstein–Barr-virus-associated gastric cancer (EBVaGC) remains to be elucidated. In this study, we used transcriptomics, metabolomics, and lipidomics to comprehensively investigate aberrant metabolism in EBVaGC. Specifically, we conducted gene expression analyses using microarray-based data from gastric adenocarcinoma epithelial cell lines and tissue samples from patients with clinically advanced gastric carcinoma. We also conducted complementary metabolomics and lipidomics using various mass spectrometry platforms. We found a significant downregulation of genes related to metabolic pathways, especially the metabolism of amino acids, lipids, and carbohydrates. The effect of dysregulated metabolic genes was confirmed in a survival analysis of 3951 gastric cancer patients. We found 57 upregulated metabolites and 31 metabolites that were downregulated in EBVaGC compared with EBV-negative gastric cancer. Sixty-nine lipids, mainly ether-linked phospholipids and triacylglycerols, were downregulated, whereas 45 lipids, mainly phospholipids, were upregulated. In total, 15 metabolisms related to polar metabolites and 15 lipid-associated pathways were involved in alteration of metabolites by EBV in gastric cancer. In this work, we have described the metabolic landscape of EBVaGC at the multi-omics level. These findings could help elucidate the mechanism of EBVaGC oncogenesis.

scholarly journals Clinical Behavior and Treatment Response of Epstein‐Barr Virus‐Positive Metastatic Gastric Cancer: Implications for the Development of Future Trials

2020 ◽  
Vol 25 (9) ◽  
pp. 780-786 ◽  
Author(s):  
Salvatore Corallo ◽  
Giovanni Fucà ◽  
Federica Morano ◽  
Massimiliano Salati ◽  
Andrea Spallanzani ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Response ◽  
Epstein Barr Virus ◽  
Metastatic Gastric Cancer ◽  
Clinical Behavior ◽  
Barr Virus ◽  
Epstein Barr
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