Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 32, Pages 13134-13139Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0706017104
Keywords
immunomodulation; microenvironment; Th2; T-reg; c-Jun
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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 (T-reg) 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-l (Gall), 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 Thl/Th2 balance. In contrast, Gall treatment of activated T cells favored the secretion of Th2 cytokines and the expansion of CD4(+)CD25(high) FOXP3(+) T-reg cells. These data directly implicate RS cell Gall in the development and maintenance of an immunosuppressive Th2/T-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.
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