THE AP1-DEPENDENT SECRETION OF GALECTIN-1 BY REED-STERNBERG CELLS FOSTERS IMMUNE PRIVILEGE IN CLASSICAL HODGKIN LYMPHOMA

PRZEMYSLAW JUSZCZYNSKI,; JING OUYANG,; JEFFERY KUTOK,; STEFANO MONTI,; WEN CHEN,; PAOLA DAL CIN,; JEREMY ABRAMSON,; KUNIHIKO TAKEYAMA,; TODD GOLUB,; JON ASTER,; GABRIEL RABINOVICH,; MARGARET SHIPP

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

National Academy of Sciences

Lugar: Washington, DC ; Año: 2007 vol. 104 p. 13134 - 13139

0027-8424

Classical Hodgkin lymphomas (cHLs) contain small numbers of neoplastic Reed-Sternberg (RS) cells within an extensive inflammatory infiltrate that includes abundant T helper (Th)-2 and T regulatory (Treg) cells. The skewed nature of the T cell infiltrate and the lack of an effective host antitumor immune response suggest that RS cells use potent mechanisms to evade immune attack. In a screen for T cell-inhibitory molecules in cHL, we found that RS cells selectively overexpressed the immunoregulatory glycan-binding protein, galectin-1 (Gal1), through an AP1-dependent enhancer. In cocultures of activated T cells and Hodgkin cell lines, RNAi-mediated blockade of RS cell Gal1 increased T cell viability and restored the Th1/Th2 balance. In contrast, Gal1 treatment of activated T cells favored the secretion of Th2 cytokines and the expansion of CD4+CD25high FOXP3+ Treg cells. These data directly implicate RS cell Gal1 in the development and maintenance of an immunosuppressive Th2/Treg-skewed microenvironment in cHL and provide the molecular basis for selective Gal1 expression in RS cells. Thus, Gal1 represents a potential therapeutic target for restoring immune surveillance in cHL.104(32):13134-9