|Publication Type||Journal Article|
|Year of Publication||2007|
|Authors||Juszczynski, P, Ouyang, J, Monti, S, Rodig, SJ, Takeyama, K, Abramson, J, Chen, W, Kutok, JL, Rabinovich, GA, Shipp, MA|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Pages||13134 - 9|
|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|
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.