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The AP1-dependent secretion of galectin-1 by Reed Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
| Publication Type | Journal Article |
| Authors | Juszczynski, Przemyslaw, Ouyang Jing, Monti Stefano, Rodig Scott J., Takeyama Kunihiko, Abramson Jeremy, Chen Wen, Kutok Jeffery L., Rabinovich Gabriel A., and Shipp Margaret A. |
| Abstract | 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. |
| Year of Publication | 2007 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 104 |
| Issue | 32 |
| Pages | 13134 - 9 |
| Date Published (YYYY/MM/DD) | 2007/08/07/ |
| ISBN Number | 0027-8424 |
| Keywords | Cancer, Cytokines, Forkhead Transcription Factors, Galectin 1, Hodgkin Disease, Humans, Immune Tolerance, Reed-Sternberg Cells, Regulatory, T-Lymphocytes, Th2 Cells, Transcription Factor AP-1 |
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