High Levels of Class I Major Histocompatibility Complex mRNA Are Present in Epstein-Barr Virus-Associated Gastric Adenocarcinomas.

Farhad Ghasemi,Steven F Gameiro,Joe S Mymryk,Tanner M Tessier,Allison H Maciver

doi:10.3390/cells9020499

Farhad Ghasemi, Steven F Gameiro + Show 3 more

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https://doi.org/10.3390/cells9020499

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Journal: Cells	Publication Date: Feb 21, 2020
Citations: 20	License type: CC BY 4.0

Affiliation: Western University, Lawson Health Research Institute

Abstract

Epstein–Barr virus (EBV) is responsible for approximately 9% of stomach adenocarcinomas. EBV-encoded microRNAs have been reported as reducing the function of the class I major histocompatibility complex (MHC-I) antigen presentation apparatus, which could allow infected cells to evade adaptive immune responses. Using data from nearly 400 human gastric carcinomas (GCs), we assessed the impact of EBV on MHC-I heavy and light chain mRNA levels, as well as multiple other components essential for antigen processing and presentation. Unexpectedly, mRNA levels of these genes were as high, or higher, in EBV-associated gastric carcinomas (EBVaGCs) compared to normal control tissues or other GC subtypes. This coordinated upregulation could have been a consequence of the higher intratumoral levels of interferon γ in EBVaGCs, which correlated with signatures of increased infiltration by T and natural killer (NK) cells. These results indicate that EBV-encoded products do not effectively reduce mRNA levels of the MHC-I antigen presentation apparatus in human GCs.

Highlights

The anti-viral immune response is composed of several layers of defenses that cooperatively contribute to blocking, controlling, and eliminating infection
Our results showed that EBV-associated gastric carcinomas (EBVaGCs) generally exhibited higher levels of all major histocompatibility complex class I (MHC-I) components compared to normal control tissues or other gastric carcinomas (GCs) subtypes
EBVaGC samples were significantly overrepresented in the high expression group for each of these seven MHC-I pathway genes compared to Epstein–Barr virus (EBV) negative GCs (p< 0.05)

Summary

Introduction

The anti-viral immune response is composed of several layers of defenses that cooperatively contribute to blocking, controlling, and eliminating infection. Subsequent antigen-specific adaptive immune responses represent an additional defense that develops with time throughout the course of infection. The cellular-mediated facet of the adaptive branch of the immune system is dependent on the recognition of intracellularly-derived viral peptides by specific cytotoxic T lymphocytes (CTLs). Intracellularly processed viral peptides are presented on the cell surface in the context of major histocompatibility complex class I (MHC-I) molecules. This membrane bound MHC-I antigen complex can crosslink with receptors present on surveilling CTLs, which triggers the necessary anti-viral mechanisms necessary to resolve infection [3]

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