Viral induction and targeted inhibition of galectin-1 in EBV+ posttransplant lymphoproliferative disorders

Blood. 2011 Apr 21;117(16):4315-22. doi: 10.1182/blood-2010-11-320481. Epub 2011 Feb 7.


Posttransplant lymphoproliferative disorders (PTLDs) are potentially fatal, EBV-driven B-cell malignancies that develop in immunocompromised solid organ or hematopoietic stem cell recipients. In PTLD, the expression of EBV proteins, including latent membrane protein 1 (LMP1) and LMP2A, viral immune evasion strategies, and impaired host immune surveillance foster the proliferation of EBV-transformed B cells. Current PTLD treatment strategies include reduction of immunosuppression, which increases the risk of graft rejection, anti-CD20 treatment, combination chemotherapy, and administration of EBV-specific cytotoxic T cells. In the present study, we report that EBV-transformed lymphoblastoid B-cell lines (LCLs) and primary PTLDs overexpress galectin-1 (Gal1), a carbohydrate-binding lectin that induces tolerogenic dendritic cells and triggers the selective apoptosis of CD4(+) Th1 and Th17 cells and cytotoxic T cells. In transcriptional reporter assays, LMP2A and LMP1 each increased Gal1-driven luciferase expression, and the combination of LMP2A and LMP1 was additive. In addition, small interfering RNA (siRNA)-mediated depletion of LMP2A decreased Gal1 protein abundance in EBV-transformed LCLs. Gal1 expression in LCLs was dependent on both activating protein 1 (AP-1) and PI3K. A newly developed neutralizing Gal1 mAb selectively inhibited Gal1-mediated apoptosis of EBV-specific CD8(+) T cells. Given the tolerogenic and immunosuppressive function of Gal1, antibody-mediated Gal1 neutralization may represent a novel immunotherapeutic strategy for PTLD and other Gal1-expressing tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Apoptosis
  • Cell Line, Transformed
  • Cell Line, Tumor
  • Cell Transformation, Viral*
  • Galectin 1 / genetics*
  • Galectin 1 / immunology
  • Gene Expression Regulation, Neoplastic
  • Herpesvirus 4, Human / physiology*
  • Humans
  • Lymphoproliferative Disorders / genetics
  • Lymphoproliferative Disorders / virology*
  • Mice
  • T-Lymphocytes, Cytotoxic / cytology
  • Transcription Factor AP-1 / metabolism
  • Up-Regulation
  • Viral Matrix Proteins / metabolism


  • Antibodies, Monoclonal
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Galectin 1
  • Transcription Factor AP-1
  • Viral Matrix Proteins