Evidence map›Paper›PMID 41923627›Full record

ArticleCell reports. Medicine2026

Epstein-Barr virus orchestrates spatial reorganization and immunomodulation in the classic Hodgkin lymphoma tumor microenvironment.

Yao Yu Yeo, Huaying Qiu, Yunhao Bai, Bokai Zhu, Yuzhou Chang, Fabio Iannelli, Stephanie Pei Tung Yiu, Jason Yeung, Hendrik A Michel, Yuchen Wang and 33 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
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

6 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

43 authors.

Yao Yu YeoCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Program in Virology, Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
Huaying QiuCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Yunhao BaiDepartment of Pathology, Stanford University, Stanford, CA, USA; Department of Chemistry, Stanford University, Stanford, CA, USA.
Bokai ZhuDepartment of Pathology, Stanford University, Stanford, CA, USA; Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA.
Yuzhou ChangCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA.
Fabio IannelliDivision of Haematopathology, European Institute of Oncology IRCCS, Milan, Italy.
Stephanie Pei Tung YiuCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Jason YeungCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Hendrik A MichelCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Program in Virology, Division of Medical Sciences, Harvard Medical School, Boston, MA, USA.
Yuchen WangCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Yang WangCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Wenrui WuCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Kyle WrightDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Muhammad ShabanDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Sam SadighDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Dingani NkosiDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Vignesh ShanmugamDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Philip RockDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Precious CramerCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Julia PaczkowskaDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Pierre StephanCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Université de Paris, Assistance Publique-Hôpitaux de Paris, Hemato-oncologie, Saint-Louis Hôspital, Paris, France.
Guanrui LiaoCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Amy Y HuangDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Hongbo WangDivision of Infectious Disease, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Han ChenDepartment of Pathology, Stanford University, Stanford, CA, USA.
Leonie FrauenfeldDepartment of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.
Louisa KaufmannDepartment of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany.
Stefano PileriDivision of Haematopathology, European Institute of Oncology IRCCS, Milan, Italy.
Bidisha MitraDivision of Infectious Disease, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Benjamin E GewurzProgram in Virology, Division of Medical Sciences, Harvard Medical School, Boston, MA, USA; Division of Infectious Disease, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Bo ZhaoDivision of Infectious Disease, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Garry P NolanDepartment of Pathology, Stanford University, Stanford, CA, USA.
Baochun ZhangDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Alex K ShalekBroad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA.
Michael AngeloDepartment of Pathology, Stanford University, Stanford, CA, USA.
Christian M SchürchDepartment of Pathology and Neuropathology, University Hospital and Comprehensive Cancer Center Tübingen, Tübingen, Germany; Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tübingen, Tübingen, Germany.
Faisal MahmoodDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Roberto ChiarleDivision of Haematopathology, European Institute of Oncology IRCCS, Milan, Italy; Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy; Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
Qin MaPelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, OH, USA; Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, USA.
W Richard BurackDepartment of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, NY, USA.
Margaret A ShippDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Scott J RodigDepartment of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Sizun JiangCenter for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Program in Virology, Division of Medical Sciences, Harvard Medical School, Boston, MA, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Pathology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: sjiang3@bidmc.harvard.edu.

Funding

Cancer Immune Monitoring and Analysis CenterU24CA224331 · NCI · DANA-FARBER CANCER INST · PI FRANK S HODI, Catherine Ju-Ying Wu · 2017 to 2026
$18.4M
Spatial-Temporal Dissection of Stratified Host Tissue Responses to Severe acute respiratory syndrome-related coronaviruses in situ to Understand Intra-host PathogenesisDP2AI171139 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI Sizun Jiang · 2022 to 2026
$2.3M
NCI NIH HHS U24 CA224331NIAID NIH HHS DP2 AI171139
6 · The paper itself

Abstract

Classic Hodgkin lymphoma (cHL) is composed of rare malignant Hodgkin and Reed-Sternberg (HRS) cells within a T-cell-rich tumor microenvironment (TME). Epstein-Barr virus (EBV) is present in ∼25% of cases, but its contribution to pathogenesis and immunomodulation remains unclear due to technical barriers. Using complementary spatial proteomics and transcriptomics across multi-institutional cohorts, we systematically map key EBV-linked TME reorganization. EBV-positive cHL exhibits distinct immunological features, including memory CD8 T cell enrichment, heightened T cell dysfunction spatially correlated with HRS proximity, and terminally exhausted T cell signatures contrasting with progenitor-exhausted patterns in EBV-negative disease. We identify EBV-encoded LMP1 as a factor in T cell dysfunction through enhanced HRS:CD8 interactions, and its expression level correlates with T cell terminal exhaustion in a distance-dependent manner. This spatial framework dissects viral-mediated immune evasion in the cHL TME, highlighting potential therapeutic opportunities to target virus-associated T cell dysfunction for precision immunotherapy in virus-associated malignancies.

Indexed as

Epstein-Barr Virus InfectionsHerpesvirus 4, HumanHodgkin DiseaseImmunomodulationTumor MicroenvironmentCD8-Positive T-LymphocytesHumansProteomicsReed-Sternberg CellsT-Cell ExhaustionViral Matrix ProteinsEBV-associated membrane antigen, Epstein-Barr virusViral Matrix ProteinsEBVHodgkin lymphomamultiplexed imagingspatial proteomicsspatial transcriptomicssystems immunologytumor microenvironmenttumor virus

Identifiers

PMID41923627
PMCPMC13130692

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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.