Evidence map›Paper›PMID 29946193›Full record

ArticleLeukemia2019

Epstein-Barr virus-encoded EBNA2 alters immune checkpoint PD-L1 expression by downregulating miR-34a in B-cell lymphomas.

Eleni Anastasiadou, Dina Stroopinsky, Stella Alimperti, Alan L Jiao, Athalia R Pyzer, Claudia Cippitelli, Giuseppina Pepe, Martina Severa, Jacalyn Rosenblatt, Marilena P Etna and 10 more

Open access · hybridAbstract read
In one paragraph

Article in Leukemia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers.

0numbers the graph read from it
0cells of the map it votes in
115citing papers in PubMed
7.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

115 citing papers in PubMed, 161 citations in OpenAlex.

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  14. Viral oncogenesis in cancer: from mechanisms to therapeutics.Signal transduction and targeted therapy · 2025
    Review
  15. Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025
    Review
  16. Article
  17. Review
  18. Review
  19. Article
  20. ImmiR: A database of microRNAs associated with immune checkpoints and infiltrates.Computational and structural biotechnology journal · 2025
    Article

55 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 3 countries.

Eleni AnastasiadouHarvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0003-0212-6734
Dina StroopinskyDepartment of Hematology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Stella AlimpertiThe Wyss Institute for Biological Inspired Engineering at Harvard, Harvard University, Boston, MA, USA.
Alan L JiaoHarvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Athalia R PyzerDepartment of Hematology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Claudia CippitelliDepartment of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Rome, Italy.
Giuseppina PepeDepartment of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Rome, Italy.
Martina SeveraDepartment of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
Jacalyn RosenblattDepartment of Hematology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Marilena P EtnaDepartment of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
Simone RiegerHelmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Marchioninistraße 25, 81377, Munich, Germany.
Bettina KempkesHelmholtz Zentrum München, Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Marchioninistraße 25, 81377, Munich, Germany.
Eliana M CocciaDepartment of Infectious Diseases, Istituto Superiore di Sanità, Rome, Italy.
Shannan J Ho SuiBioinformatics Core, Harvard T. H. Chan School of Public Health, Boston, MA, 02115, USA.
Christopher S ChenThe Wyss Institute for Biological Inspired Engineering at Harvard, Harvard University, Boston, MA, USA.
Stefania UcciniDepartment of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University, Rome, Italy.
David AviganDepartment of Hematology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Alberto FaggioniDepartment of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 0161, Rome, Italy.
Pankaj TrivediDepartment of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 0161, Rome, Italy. Pankaj.trivedi@uniroma1.it.
Frank J SlackHarvard Medical School Initiative for RNA Medicine, Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. fslack@bidmc.harvard.edu.ORCID http://orcid.org/0000-0001-8263-0409
Beth Israel Deaconess Medical Center · USHarvard University · USIstituto Superiore di Sanità · ITHelmholtz Zentrum München · DESapienza University of Rome · IT

Funding

Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
NCATS NIH HHS UL1 TR001102
6 · The paper itself

Abstract

Cancer cells subvert host immune surveillance by altering immune checkpoint (IC) proteins. Some Epstein-Barr virus (EBV)-associated tumors have higher Programmed Cell Death Ligand, PD-L1 expression. However, it is not known how EBV alters ICs in the context of its preferred host, the B lymphocyte and in derived lymphomas. Here, we found that latency III-expressing Burkitt lymphoma (BL), diffuse large B-cell lymphomas (DLBCL) or their EBNA2-transfected derivatives express high PD-L1. In a DLBCL model, EBNA2 but not LMP1 is sufficient to induce PD-L1. Latency III-expressing DLBCL biopsies showed high levels of PD-L1. The PD-L1 targeting oncosuppressor microRNA miR-34a was downregulated in EBNA2-transfected lymphoma cells. We identified early B-cell factor 1 (EBF1) as a repressor of miR-34a transcription. Short hairpin RNA (shRNA)-mediated knockdown of EBF1 was sufficient to induce miR-34a transcription, which in turn reduced PD-L1. MiR-34a reconstitution in EBNA2-transfected DLBCL reduced PD-L1 expression and increased its immunogenicity in mixed lymphocyte reactions (MLR) and in three-dimensional biomimetic microfluidic chips. Given the importance of PD-L1 inhibition in immunotherapy and miR-34a dysregulation in cancers, our findings may have important implications for combinatorial immunotherapy, which include IC inhibiting antibodies and miR-34a, for EBV-associated cancers.

Indexed as

B7-H1 AntigenBiomarkers, TumorEpstein-Barr Virus InfectionsEpstein-Barr Virus Nuclear AntigensGene Expression Regulation, NeoplasticHerpesvirus 4, HumanHumansLymphoma, Large B-Cell, DiffuseMicroRNAsPrognosisT-LymphocytesTumor Cells, CulturedViral ProteinsB7-H1 AntigenBiomarkers, TumorCD274 protein, humanEBNA-2 protein, Human herpesvirus 4Epstein-Barr Virus Nuclear AntigensMicroRNAsMIRN34 microRNA, humanViral Proteins

Identifiers

PMID29946193
PMCPMC6327052
OpenAlexW2811453807

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.