1. STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides.
- Author
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Fredholm S, Gjerdrum LM, Willerslev-Olsen A, Petersen DL, Nielsen IØ, Kauczok CS, Wobser M, Ralfkiaer U, Bonefeld CM, Wasik MA, Krejsgaard T, Geisler C, Ralfkiaer E, Gniadecki R, Woetmann A, and Odum N
- Subjects
- Biopsy, Cell Line, Tumor, Gene Knockout Techniques, HMGB1 Protein genetics, HMGB1 Protein metabolism, Humans, Immunohistochemistry, Interleukin-5 genetics, Interleukin-5 metabolism, Mycosis Fungoides genetics, Mycosis Fungoides immunology, RNA Interference, STAT3 Transcription Factor genetics, T-Lymphocytes immunology, T-Lymphocytes metabolism, T-Lymphocytes pathology, Eosinophils pathology, Mycosis Fungoides metabolism, Mycosis Fungoides pathology, STAT3 Transcription Factor metabolism
- Abstract
Eosinophil granulocytes have been implicated in anticancer immunity but recent data indicate that eosinophils can also promote cancer. Herein, we studied eosinophils in skin lesions from 43 patients with mycosis fungoides (MF). The presence of eosinophils correlated with disease stage: 78% of patients with advanced disease displayed eosinophil infiltration, whereas this was only seen in 11% of patients with patches (p<0.01), and in 48% of those with plaque disease. Importantly, 72% of patients with positive staining for phospho-signal-transducer-and-activator-of-transcription (pY-STAT3) in malignant T-cells also stained positively for eosinophils, whereas this was only observed in 28% of pY-STAT3-negative patients (p<0.01). Notably, malignant T-cells expressed eosinophilic activation and trafficking factors: High-mobility group BOX-1 protein (HMGB1) and interleukin 5 (IL5). STAT3 siRNA profoundly inhibited IL5 but not HMGB1 expression. In conclusion, these data suggest that malignant T-cells orchestrate accumulation and activation of eosinophils supporting the notion of STAT3 being a putative target for therapy., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2014