Role of IL-13 and its receptors in the pathogenesis of cutaneous T-cell lymphomas (TUM7P.961)

Cutaneous T-cell lymphomas (CTCL) affect primarily skin and are characterized by proliferation of mature CD4+ T-helper cells. Diagnose is difficult in the absence of specific markers for malignant lymphocytes. The pattern of cytokine production in the skin and blood is considered to be of major importance for the pathogenesis of CTCL. Abnormal cytokine expression in CTCL may be responsible for enhanced proliferation of the malignant cells and/or the depression of the anti-tumor immune response. Cytokine IL-13 promotes growth or survival of several tumors as well as suppresses immunosurveillance. Here we show that IL-13 and its receptors IL-13Rα1 and IL-13Rα2 are highly expressed in the clinically involved skin of CTCL patients. We also show that the tumor cells, identified by the expression of CD4 and TOX (thymus high-mobility group box), in the skin and blood of CTCL patients produce IL-13 and express both receptors. This finding is intriguing since CTCL is a T-cell origin tumor yet T cells do not express IL-13 receptors. Thus IL-13 is implicated as a possible autocrine factor for CTCL. Furthermore expression of the decoy IL-13Rα2 by CTCL cells may represent a novel marker of CTCL malignancy. Soluble human IL-13Rα2 and an anti-IL-13 monoclonal antibody are being tested for inhibition of tumor cell proliferation in the peripheral blood of patients. Altogether these results identify potential tumor markers for the early diagnosis of CTCL as well as novel therapeutic targets.