MSI and EBV Positive Gastric Cancer’s Subgroups and Their Link with Novel Immunotherapy

Rodriquenz, Maria Grazia; Roviello, Giandomenico; D’Angelo, Alberto; Lavacchi, Daniele; Roviello, Franco; Połom, Karol

doi:10.3390/jcm9051427

Cited by 61 publications

(46 citation statements)

References 52 publications

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“…In GCLS, EBV-positive tumors had more PI3K/AKT pathway mutations than EBV-negative tumors [ 80 ]. In addition, because EBVaGCs are significantly correlated with high TILs, new immunotherapeutic strategies associated with T-cells are challenging for the treatment of advanced EBVaGCs [ 81 , 82 ]. ARID1A expression was higher in EBVaGCs than in non-EBVaGCs.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

2020

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Background and objectives: The present study aims to elucidate the clinicopathologic significance of Epstein–Barr virus (EBV) infection in gastric carcinomas (GCs) through a meta-analysis. Materials and Methods: Sixty-one eligible studies were included in the present meta-analysis. The included patients, with and without EBV infection, were 2063 and 17,684, respectively. We investigated the clinicopathologic characteristics and various biomarkers, including programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes (TILs). Results: The estimated EBV-infected rate of GCs was 0.113 (95% confidence interval (CI): 0.088–0.143). The EBV infection rates in GC cells were 0.138 (95% CI: 0.096–0.194), 0.103 (95% CI: 0.077–0.137), 0.080 (95% CI: 0.061–0.106), and 0.042 (95% CI: 0.016–0.106) in the population of Asia, America, Europe, and Africa, respectively. There was a significant difference between EBV-infected and noninfected GCs in the male: female ratio, but not other clinicopathological characteristics. EBV infection rates were higher in GC with lymphoid stroma (0.573, 95% CI: 0.428–0.706) than other histologic types of GCs. There were significant differences in high AT-rich interactive domain-containing protein 1A (ARID1A) and PD-L1 expressions, and high CD8+ TILs between EBV-infected and noninfected GCs. Conclusions: Our results showed that EBV infection of GCs was frequently found in male patients and GCs with lymphoid stroma. EBV infection was significantly correlated with ARID1A and PD-L1 expressions and CD8+ TILs in GCs.

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Section: Discussionmentioning

confidence: 99%

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

2020

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“…Over 90% of the world population is latent infected throughout life with the Epstein–Barr Virus (EBV), accounting for 9% in all gastric adenocarcinomas [ 40 ]. Analysis of the TCGA (The Cancer Genome Atlas) cohort shows evidence of EBV in overall gastric cancer patients of 8.2% with predominance in male patients (81%), young patients, gastric fundus, or body independent from histological subtype [ 41 , 42 ]. EBV-positive gastric cancers reveal a higher expression of immune checkpoint genes (e.g., PD-1, CTLA-4) and higher histological lymphocytic infiltration compared with MSS(microsatellite-stable) tumours [ 43 ].…”

Section: Role Of Biomarkers In Oesophago-gastric Cancers (Pd-l1 Cpmentioning

confidence: 99%

Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

Högner

Thuss‐Patience

2021

Pharmaceuticals

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Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.

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“…The Cancer Genome Atlas reports a comprehensive identification of genetic changes associated with gastric cancer and further divides this form of cancer into four subtypes: EBV-positive tumors (9%), microsatellite unstable tumors (22%), genetically stable tumors (20%), and chromosome unstable tumors (50%). Moreover, EBV-positive and MSI gastric cancers have the capability to respond to newer immunotherapy drugs ( 17 ). However, as opposed to general gastric cancer, EBV-positive gastric cancer, despite having unique pathological characteristics, has no specific clinical manifestations.…”

Section: Characteristics Of Ebv-positive Gastric Cancermentioning

confidence: 99%

EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives

Sun

Jia

et al. 2020

Front. Oncol.

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Gastric cancer is the fifth most common malignant tumor and second leading cause of cancer-related deaths worldwide. With the improved understanding of gastric cancer, a subset of gastric cancer patients infected with Epstein–Barr virus (EBV) has been identified. EBV-positive gastric cancer is a type of tumor with unique genomic aberrations, significant clinicopathological features, and a good prognosis. After EBV infects the human body, it first enters an incubation period in which the virus integrates its DNA into the host and expresses the latent protein and then affects DNA methylation through miRNA under the action of the latent protein, which leads to the occurrence of EBV-positive gastric cancer. With recent developments in immunotherapy, better treatment of EBV-positive gastric cancer patients appears achievable. Moreover, studies show that treatment with immunotherapy has a high effective rate in patients with EBV-positive gastric cancer. This review summarizes the research status of EBV-positive gastric cancer in recent years and indicates areas for improvement of clinical practice.

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MSI and EBV Positive Gastric Cancer’s Subgroups and Their Link with Novel Immunotherapy

Cited by 61 publications

References 52 publications

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

Clinicopathological Significance of EBV-Infected Gastric Carcinomas: A Meta-Analysis

Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives

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