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

• Published in: Blood Vol. 110; no. 4; pp. 1326 - 1329
• Main Authors: Gandhi, Maher K., Moll, Guido, Smith, Corey, Dua, Ujjwal, Lambley, Eleanore, Ramuz, Olivier, Gill, Devinder, Marlton, Paula, Seymour, John F., Khanna, Rajiv
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.08.2007; The Americain Society of Hematology; American Society of Hematology
• Series: Neoplasia
• Subjects: Adult; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Epstein-Barr Virus Infections - genetics; Epstein-Barr Virus Infections - metabolism; Epstein-Barr Virus Infections - virology; Female; Galectin 1 - metabolism; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - genetics; Herpesvirus 4, Human - metabolism; Hodgkin Disease - immunology; Hodgkin Disease - metabolism; Hodgkin Disease - virology; Humans; Interferon-gamma - metabolism; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphocytes, Tumor-Infiltrating - metabolism; Male; Medical sciences; Neoplasia; Recombinant Proteins - genetics; Recombinant Proteins - isolation & purification; Recombinant Proteins - metabolism; Reed-Sternberg Cells - immunology; Reed-Sternberg Cells - metabolism; T-Lymphocytes; Gammaherpesvirinae; Human; Acquired immunity; Herpesviridae; Hodgkin disease; Malignant hemopathy; Epstein Barr virus; Lymphoma; Infection; Virus; Immunosuppression; Lymphoproliferative syndrome; Viral disease; T-Lymphocyte; Suppressive cell; Galectin 1; CD8 T lymphocyte
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2007-01-066100

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.