Human Cancer Biology IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma

Purpose: Both patients with cutaneous T-cell lymphoma (CTCL) and those with atopic dermatitis (AD) have pruritus, TH2-biased T cells, and a tendency to have bacterial infections, suggesting a common pathologic basis for these two diseases. Recently, interleukin (IL)-22–producing T cells were reported in skin of patients with AD. In this study, we investigated expression levels of TH22and TH17-relatedmolecules in lesional skin and sera isolated from patients with CTCL. Experimental Design: Skin biopsies and sera were collected from patients with CTCL or psoriasis and fromhealthy volunteers. Protein andmRNAexpression levels of IL-22, IL-17A, IL-17F, IL-23p19, IL-10, IL-4, CCL20, CCR6, IL-8, and IL-20 were examined in lesional tissue and a subset of these molecules in sera. Phosphorylation of STAT3 was also assessed in lesional skin of CTCL and psoriasis by immunohistochemistry. Results: IL-22, IL-10, IL-4, CCL20, andCCR6mRNAandprotein levels, but not IL-17A, IL-17F, IL-23p19, IL-8, or IL-20,were significantly elevated in lesional skin ofCTCL. Phosphorylation of STAT3wasdetected in epidermis of CTCL skin. Moreover, serum IL-22, IL-10, and CCL20 levels were increased in CTCL and correlated with disease severity. Conclusions:Our results suggest that IL-22 is important in establishing the tumormicroenvironment for CTCL. Enhanced expression of CCL20 may explain epidermal hyperplasia and migration of CCR6þ cells, such as Langerhans cells, into lesional skin. Relatively low expression of IL-17 may explain the lack of neutrophils in lesions of CTCL, which correlates with bacterial infections that commonly occur in skin affected by CTCL. Clin Cancer Res; 17(24); 7529–38. 2011 AACR.