Page 67 - Read Online

Miliotis et al. J Cancer Metastasis Treat 2020;6:13 Journal of Cancer
DOI: 10.20517/2394-4722.2020.12 Metastasis and Treatment

Review Open Access

Multi-layered control of PD-L1 expression in
Epstein-Barr virus-associated gastric cancer

Christos N. Miliotis, Frank J. Slack

HMS Initiative for RNA Medicine, Department of Pathology, Cancer Center, Beth Israel Deaconess Medical Center, Harvard
Medical School, Boston, MA 02115, USA.
Correspondence to: Dr. Frank J. Slack, Department of Pathology, Cancer Center, Beth Israel Deaconess Medical Center, Harvard
Medical School, 3 Blackfan Circle, Boston, MA 02115, USA. E-mail: fslack@bidmc.harvard.edu
How to cite this article: Miliotis CN, Slack FJ. Multi-layered control of PD-L1 expression in Epstein-Barr virus-associated gastric
cancer. J Cancer Metastasis Treat 2020;6:13. http://dx.doi.org/10.20517/2394-4722.2020.12
Received: 1 Feb 2020 First Decision: 7 Apr 2020 Revised: 23 Apr 2020 Accepted: 12 May 2020 Published: 23 May 2020

Science Editor: Pravin D. Potdar Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract
Gastric cancer (GC) is the fifth most common cancer worldwide. In approximately 10% of GC cases, cancer cells
show ubiquitous and monoclonal Epstein-Barr virus (EBV) infection. A significant feature of EBV-associated
GC (EBVaGC) is high lymphocytic infiltration and high expression of immune checkpoint proteins, including
programmed death-ligand 1 (PD-L1). This highlights EBVaGC as a strong candidate for immune checkpoint
blockade therapy. Indeed, several recent studies have shown that EBV positivity in GC correlates with positive
response to programmed cell death protein 1 (PD-1)/PD-L1 blockade therapy. Understanding the mechanisms
that control PD-L1 expression in EBVaGC can indicate new predictive biomarkers for immunotherapy, as well
as therapeutic targets for combination therapy. Various mechanisms have been implicated in PD-L1 expression
regulation, including structural variations, post-transcriptional control, oncogenic activation of intrinsic signaling
pathways, and increased sensitivity to extrinsic signals. This review provides the most recent updates on the multi-
layered control of PD-L1 expression in EBVaGC.

Keywords: Epstein-Barr virus, gastric cancer, immunotherapy, programmed death-ligand 1

INTRODUCTION
[1]
Gastric cancer (GC) is the fifth most common and third most deadly cancer worldwide . Due to the
lack of early symptoms, patients are usually diagnosed with locally advanced or metastatic cancer, when

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

www.jcmtjournal.com