Multi-modal analysis reveals tumor and immune features distinguishing EBV-positive and EBV-negative post-transplant lymphoproliferative disorders

Cell Rep Med. 2024 Dec 17;5(12):101851. doi: 10.1016/j.xcrm.2024.101851. Epub 2024 Dec 9.

Abstract

The oncogenic Epstein-Barr virus (EBV) can drive tumorigenesis with disrupted host immunity, causing malignancies including post-transplant lymphoproliferative disorders (PTLDs). PTLD can also arise in the absence of EBV, but the biological differences underlying EBV(+) and EBV(-) B cell PTLD and the associated host-EBV-tumor interactions remain poorly understood. Here, we reveal the core differences between EBV(+) and EBV(-) PTLD, characterized by increased expression of genes related to immune processes or DNA interactions, respectively, and the augmented ability of EBV(+) PTLD B cells to modulate the tumor microenvironment through elaboration of monocyte-attracting cytokines/chemokines. We create a reference resource of proteins distinguishing EBV(+) B lymphoma cells from EBV(-) B lymphoma including the immunomodulatory molecules CD300a and CD24, respectively. Moreover, we show that CD300a is essential for maximal survival of EBV(+) PTLD B lymphoma cells. Our comprehensive multi-modal analyses uncover the biological underpinnings of PTLD and offer opportunities for precision therapies.

Keywords: B cell lymphoma; CD300a; Epstein-Barr virus; multi-cohort analysis; multi-omics; post-transplant lymphoproliferative disorder; tumor microenvironment; tumor-immune interactions.

MeSH terms

  • B-Lymphocytes / immunology
  • CD24 Antigen / genetics
  • CD24 Antigen / immunology
  • CD24 Antigen / metabolism
  • Epstein-Barr Virus Infections* / immunology
  • Epstein-Barr Virus Infections* / virology
  • Herpesvirus 4, Human* / immunology
  • Herpesvirus 4, Human* / pathogenicity
  • Humans
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / pathology
  • Lymphoma, B-Cell / virology
  • Lymphoproliferative Disorders* / immunology
  • Lymphoproliferative Disorders* / pathology
  • Lymphoproliferative Disorders* / virology
  • Tumor Microenvironment / immunology

Substances

  • CD24 Antigen