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Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

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Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
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Author Spotlight: Unlocking Insights into the Immune Cell Landscape of Tumors
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Spatial transcriptomics reveals tumor microenvironment heterogeneity in EBV positive diffuse large B cell lymphoma.

Mei-Yao He1, Meng Liu2, Jiayin Yuan1

  • 1Department of Pathology, The First People's Hospital of Foshan, Foshan, 528000, People's Republic of China.

Scientific Reports
|May 7, 2025
PubMed
Summary

Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma (EBV+DLBCL) exhibits an immunosuppressive tumor microenvironment (TME). Targeting PD-1/PD-L1 signaling suppressed EBV+DLBCL cell growth, suggesting a potential therapeutic strategy.

Keywords:
DLBCLEBV infectionPD-1/PD-L1Spatial transcriptomicsTME

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Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Epstein-Barr Virus-positive Diffuse Large B-cell Lymphoma (EBV+DLBCL) is linked to immune dysfunction and tumor microenvironment (TME) heterogeneity.
  • The prognostic significance of the TME in EBV-DLBCL is known, but its effect on EBV+DLBCL survival requires clarification.

Purpose of the Study:

  • To investigate the TME heterogeneity in EBV+DLBCL using integrated spatial and single-cell transcriptomics.
  • To identify key molecular pathways within the TME that influence EBV+DLBCL prognosis and therapeutic response.

Main Methods:

  • Integrated 10X Visium spatial transcriptomics (ST) and single-cell RNA sequencing (scRNA-seq) to map TME.
  • Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses.
  • Functional validation of PD-1/PD-L1 blockade using BMS202 inhibitor in EBV+Farage cells.

Main Results:

  • Spatial transcriptomics revealed significant TME heterogeneity in EBV+DLBCL.
  • PD-1/PD-L1 signaling was identified as a key pathway in the immunosuppressive TME of EBV+DLBCL.
  • BMS202 treatment inhibited EBV+DLBCL cell proliferation and induced apoptosis, with TLR4 identified as a downstream effector.

Conclusions:

  • TME-driven PD-1/PD-L1 activation is associated with poor prognosis in EBV+DLBCL.
  • PD-1/PD-L1 blockade demonstrates preclinical efficacy against EBV+DLBCL.
  • TLR4 plays a role in EBV-status-dependent regulation within the TME.