Galectin-1 mediated suppression of Epstein-Barr virus–specific T-cell immunity in classic Hodgkin lymphoma

MK Gandhi, G Moll, C Smith, U Dua… - Blood, The Journal …, 2007 - ashpublications.org
MK Gandhi, G Moll, C Smith, U Dua, E Lambley, O Ramuz, D Gill, P Marlton, JF Seymour
Blood, The Journal of the American Society of Hematology, 2007ashpublications.org
In Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg cells interact with the
host microenvironment to create an immunosuppressive network that protects the lymphoma
from immune attack. These mechanisms are not fully understood. We examined the role of
the immunomodulatory protein galectin-1 (Gal-1) on Epstein-Barr virus-specific CD8+ T cell
responses in HL. Initial studies indicated Gal-1 expression in all in vitro established Hodgkin
Reed-Sternberg cell lines. In situ analysis revealed Gal-1 expression in 26 of 42 classic HL …
Abstract
In Hodgkin lymphoma (HL), the malignant Hodgkin Reed-Sternberg cells interact with the host microenvironment to create an immunosuppressive network that protects the lymphoma from immune attack. These mechanisms are not fully understood. We examined the role of the immunomodulatory protein galectin-1 (Gal-1) on Epstein-Barr virus-specific CD8+ T cell responses in HL. Initial studies indicated Gal-1 expression in all in vitro established Hodgkin Reed-Sternberg cell lines. In situ analysis revealed Gal-1 expression in 26 of 42 classic HL, whereas Gal-1 was uniformly negative in nodular lymphocyte predominant HL. Gal-1hi expression was associated with male gender, older patients, reduced CD8+ T cell infiltration at the tumor site, and most importantly, an impaired latent membrane protein 1 and 2-specific CD8+ T-cell responses. In vitro exposure to recombinant Gal-1 inhibited proliferation and interferon-γ expression by Epstein-Barr virus-specific T cells. These observations provide an important link between the Gal-1-mediated immunomodulatory networks and loss of antigen-specific T-cell function in classic HL.
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