Scientific Publications

The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma

Publication TypeJournal Article
AuthorsJuszczynski, Przemyslaw, Ouyang Jing, Monti Stefano, Rodig Scott J., Takeyama Kunihiko, Abramson Jeremy, Chen Wen, Kutok Jeffery L., Rabinovich Gabriel A., and Shipp Margaret A.
AbstractClassical 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.
Year of Publication2007
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue32
Pages13134 - 9
Date Published (YYYY/MM/DD)2007/08/07/
ISBN Number0027-8424
KeywordsCancer, Cytokines, Forkhead Transcription Factors, Galectin 1, Hodgkin Disease, Humans, Immune Tolerance, Reed-Sternberg Cells, Regulatory, T-Lymphocytes, Th2 Cells, Transcription Factor AP-1