1. The AP1-dependent secretion of galectin-1 by Reed-Sternberg cells fosters immune privilege in classical Hodgkin lymphoma
- Author
-
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.
- Subjects
Hodgkin's disease -- Physiological aspects ,T cells -- Evaluation ,Binding proteins -- Genetic aspects ,Immunology -- Research ,Science and technology - 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 Gall 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 CD[4.sup.+]CD[25.sup.high] FOXP[3.sup.+] [T.sub.reg] cells. These data directly implicate RS cell Gall in the development and maintenance of an immunosuppressive Th2/[T.sub.reg]-skewed microenvironment in cHL and provide the molecular basis for selective Gall expression in RS cells. Thus, Gall represents a potential therapeutic target for restoring immune surveillance in cHL. immunomodulation | microenvironment | Th2 | [T.sub.reg] | c-Jun
- Published
- 2007