EBV microRNA-BHRF1-2-5p targets the 3′UTR of immune checkpoint ligands PD-L1 and PD-L2

Cristino, Alexandre S.; Nourse, Jamie P.; West, Rachael A.; Sabdia, Muhammed B.; Law, Soi Cheng; Gunawardana, Jay; Vari, Frank; Mujaj, Sally; Thillaiyampalam, Gayathri; Snell, Cameron; Gough, Madeline; Keane, Colm; Gandhi, Maher K.

doi:10.1182/blood.2019000889

Cited by 51 publications

(43 citation statements)

References 69 publications

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“…This indicates that regulation of PD-L1 by miRNAs is very strong, and cells that acquire resistance to these miRNAs could evade host immunity by increasing PD-L1 expression and proliferate as cancers. Interestingly, EBV also encodes an miRNA (miR-BHRF1-2-5p) that negatively regulates PD-L1 expression through binding to the 3 -UTR of PD-L1 mRNA [53]. On the other hand, another study demonstrated that EBV miR-BART-5-5p downregulated PIAS3, a negative regulator of STAT, and thereby upregulated PD-L1 expression in GC [54].…”

Section: Ebvmentioning

confidence: 99%

Human Herpesvirus and the Immune Checkpoint PD-1/PD-L1 Pathway: Disorders and Strategies for Survival

Murata

2021

Microorganisms

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The immune system has evolved as a complex and efficient means of coping with extrinsic materials, such as pathogens and toxins, as well as intrinsic abnormalities, such as cancers. Although rapid and timely activation of the immune system is obviously important, regulated downregulation of the system is almost as significant as activation to prevent runaway immunity, such as allergies and hypercytokinemia. Therefore, the immune checkpoint programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway is beneficial for the host. On the other hand, pathogens have evolved to evade host immunity by taking advantage of the PD-1/PD-L1 pathway. This review is focused on human herpesviruses, such as herpes simplex virus (HSV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV), which cause various types of disorders, and their relationships with the PD-1/PD-L1 pathway. Understanding such relationships will be useful for developing preventative and therapeutic methods for disorders caused by herpesviruses.

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Section: Ebvmentioning

confidence: 99%

Human Herpesvirus and the Immune Checkpoint PD-1/PD-L1 Pathway: Disorders and Strategies for Survival

Murata

2021

Microorganisms

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“…Cristino et al reported that when LMP1 was activated, PD-L1 and PD-L2 expression was significantly increased during the transformation of B cells from the late germinal center to early and late activated B cells. Moreover, microRNA-BHRF1-2-5p plays a regulatory role in LMP1 driven PD-L1 and PD-L2 amplification (39). So further identification of microRNAs that target immune checkpoints allow RNA-based therapy.…”

Section: Pd-l2mentioning

confidence: 99%

B7 Family Members in Lymphoma: Promising Novel Targets for Tumor Immunotherapy?

et al. 2021

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T cells play a vital role in the immune responses against tumors. Costimulatory or coinhibitory molecules regulate T cell activation. Immune checkpoint inhibitors, such as programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) have shown remarkable benefits in patients with various tumor, but few patients have displayed significant immune responses against tumors after PD-1/PD-L1 immunotherapy and many have been completely unresponsive. Thus, researchers must explore novel immune checkpoints that trigger durable antitumor responses and improve clinical outcomes. In this regard, other B7 family checkpoint molecules have been identified, namely PD-L2, B7-H2, B7-H3, B7-H4 and B7-H6. The aim of the present article was to address the expression, clinical significance and roles of B7 family molecules in lymphoma, as well as in T and NK cell-mediated tumor immunity. B7 family checkpoints may offer novel and immunotherapeutic strategies for patients with lymphoma.

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“…The most frequent inhibitory signal found in EBV-positive gastric cancer is high PD-L1 expression resulting from 9p24.1 amplification (about 11% of cases) [ 134 ], which leads to immune resistance and reduced survival of patients [ 135 ]. EBV gene expression may directly regulate PD-L1 and PD-L2 gene expression [ 136 , 137 ]. The mechanisms by which EBV reduces PD-L1 expression remain to be elucidated in EBVaGC, since EBV LMP-1 and EBNA-2 genes, which can increase PD-L1 expression, are not expressed in EBVaGC.…”

Section: Targeted Therapies For Ebv + Gcmentioning

confidence: 99%

Overview of Epstein–Barr-Virus-Associated Gastric Cancer Correlated with Prognostic Classification and Development of Therapeutic Options

Brisotto

Repetto

et al. 2020

IJMS

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Gastric cancer (GC) is a deadly disease with poor prognosis that is characterized by heterogeneity. New classifications based on histologic features, genotypes, and molecular phenotypes, for example, the Cancer Genome Atlas subtypes and those by the Asian Cancer Research Group, help understand the carcinogenic differences in GC and have led to the identification of an Epstein–Barr virus (EBV)-related GC subtype (EBVaGC), providing new indications for tailored treatment and prognostic factors. This article provides a review of the features of EBVaGC and an update on the latest insights from EBV-related research with a particular focus on the strict interaction between EBV infection and the gastric tumor environment, including the host immune response. This information may help increase our knowledge of EBVaGC pathogenesis and the mechanisms that sustain the immune response of patients since this mechanism has been demonstrated to offer a survival advantage in a proportion of patients with GC.

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EBV microRNA-BHRF1-2-5p targets the 3′UTR of immune checkpoint ligands PD-L1 and PD-L2

Cited by 51 publications

References 69 publications

Human Herpesvirus and the Immune Checkpoint PD-1/PD-L1 Pathway: Disorders and Strategies for Survival

Human Herpesvirus and the Immune Checkpoint PD-1/PD-L1 Pathway: Disorders and Strategies for Survival

B7 Family Members in Lymphoma: Promising Novel Targets for Tumor Immunotherapy?

Overview of Epstein–Barr-Virus-Associated Gastric Cancer Correlated with Prognostic Classification and Development of Therapeutic Options

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