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

Mikhail Y Salnikov; Katelyn M MacNeil; Joe S Mymryk

doi:10.3389/fimmu.2024.1358511

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

Front Immunol. 2024 Mar 26:15:1358511. doi: 10.3389/fimmu.2024.1358511. eCollection 2024.

Authors

Mikhail Y Salnikov¹, Katelyn M MacNeil¹, Joe S Mymryk^{1

2

3

4}

Affiliations

¹ Department of Microbiology and Immunology, Western University, London, ON, Canada.
² Department of Oncology, Western University, London, ON, Canada.
³ Department of Otolaryngology, Western University, London, ON, Canada.
⁴ Lawson Health Research Institute, London, ON, Canada.

Abstract

Epstein-Barr virus (EBV) is a pathogen known to cause a number of malignancies, often taking years for them to develop after primary infection. EBV-associated gastric cancer (EBVaGC) is one such malignancy, and is an immunologically, molecularly and pathologically distinct entity from EBV-negative gastric cancer (EBVnGC). In comparison with EBVnGCs, EBVaGCs overexpress a number of immune regulatory genes to help form an immunosuppressive tumor microenvironment (TME), have improved prognosis, and overall have an "immune-hot" phenotype. This review provides an overview of the histopathology, clinical features and clinical outcomes of EBVaGCs. We also summarize the differences between the TMEs of EBVaGCs and EBVnGCs, which includes significant differences in cell composition and immune infiltration. A list of available EBVaGC and EBVnGC gene expression datasets and computational tools are also provided within this review. Finally, an overview is provided of the various chemo- and immuno-therapeutics available in treating gastric cancers (GCs), with a focus on EBVaGCs.

Keywords: EBVaGC; Epstein-Barr virus; gastric cancer; immune landscape; immunotherapy; therapeutics; tumor microenvironment; tumor virus.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Epstein-Barr Virus Infections*
Herpesvirus 4, Human / physiology
Humans
Pathology, Clinical*
Prognosis
Stomach Neoplasms* / genetics
Stomach Neoplasms* / therapy
Tumor Microenvironment

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by a grant from the Canadian Institutes of Health Research (PJT-173496).