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Cited by 195Viral-associated cancers and disordersMicroRNA in disease regulationCancer Immunotherapy and Biomarkers

EBV miRNAs BART11 and BART17-3p promote immune escape through the enhancer-mediated transcription of PD-L1

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Wang, Jie, Ge, Junshang, Wang, Yian, Xiong, Fang, Guo, Jiayue, Jiang, Xianjie, Zhang, Lishen, Deng, Xiangying +14 more·2022·Nature Communications
DOI 10.1038/s41467-022-28479-2PMC PMC8844414
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Abstract

Epstein-Barr virus (EBV) is reportedly the first identified human tumor virus, and is closely related to the occurrence and development of nasopharyngeal carcinoma (NPC), gastric carcinoma (GC), and several lymphomas. PD-L1 expression is elevated in EBV-positive NPC and GC tissues; however, the specific mechanisms underlying the EBV-dependent promotion of PD-L1 expression to induce immune escape warrant clarification. EBV encodes 44 mature miRNAs. In this study, we find that EBV-miR-BART11 and EBV-miR-BART17-3p upregulate the expression of PD-L1 in EBV-associated NPC and GC. Furthermore, EBV-miR-BART11 targets FOXP1, EBV-miR-BART17-3p targets PBRM1, and FOXP1 and PBRM1 bind to the enhancer region of PD-L1 to inhibit its expression. Therefore, EBV-miR-BART11 and EBV-miR-BART17-3p inhibit FOXP1 and PBRM1, respectively, and enhance the transcription of PD-L1 (CD274, http://www.ncbi.nlm.nih.gov/gene/29126), resulting in the promotion of tumor immune escape, which provides insights into potential targets for EBV-related tumor immunotherapy.

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  • EBV reduces ICI effectiveness through mechanisms such as increasing PD-L1 expression, linking to CD8+ T cell exhaustion, and recruiting immunosuppressive factors.

    “These findings align with prior studies indicating that EBV reduces ICI effectiveness through mechanisms such as increasing PD-L1 expression, linking to CD8 + T cell exhaustion, and recruiting immunosuppressive factors110–113.”

    From Microbiome meets immunotherapy: unlocking the hidden predictors of immune checkpoint inhibitors (2025) · cites this paper as [112]

    The Results and Discussion (page numbers unavailable) support EBV-miRNA-driven PD-L1 upregulation and reduced T-cell killing. The mouse Results report CD8+ T-cell apoptosis, not exhaustion, and do not show recruitment of immunosuppressive factors. They also show that atezolizumab diminished the miRNA-associated differences, rather than demonstrating reduced ICI effectiveness. (LLM, conf=0.88)

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References 68 · Cited by 195

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Authors
Wang, J., Ge, J., Wang, Y., Xiong, F., Guo, J., Jiang, X., Zhang, L., Deng, X., Gong, Z., Zhang, S., Yan, Q., He, Y., Li, X., Shi, L., Guo, C., Wang, F., Li, Z., Zhou, M., Xiang, B., Li, Y., Xiong, W., & Zeng, Z.
Affiliations
  • Central South University (CN)
  • Baylor College of Medicine (US)
Corresponding author
  • Xiong, Wei
  • Zeng, Zhaoyang
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2022-02-14
Volume
13
Issue
1
Pages
866-866
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-022-28479-2
PMC
PMC8844414
OpenAlex
W4213078175
Cited by
195
References
68
Citations by year
2026: 39 · 2025: 40 · 2024: 58 · 2023: 37 · 2022: 20
FWCI
17.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81972776, 81772928, U21A20382, 82073135)
Topics
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Keywords
Epstein-Barr virus, microRNA, PD-L1, immune evasion, FOXP1, PBRM1, nasopharyngeal carcinoma, gastric cancer, cancer immunotherapy, viral oncogenesis
MeSH terms
Nasopharyngeal Carcinoma, DNA-Binding Proteins, Herpesvirus 4, Human, Humans, Lymphoma, Nasopharyngeal Neoplasms, Repressor Proteins, Stomach Neoplasms, Transcription Factors, Gene Expression Regulation, Neoplastic, Tumor Escape, Epstein-Barr Virus Infections, MicroRNAs, Cell Line, Tumor, Cell Proliferation, Forkhead Transcription Factors, Tumor Microenvironment, B7-H1 Antigen

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