STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides

Simon Fredholm, Lise Mette R. Gjerdrum, Andreas Willerslev-Olsen, David L. Petersen, Inger Nielsen, Claudia S. Kauczok, Marion Wobser, Ulrik Ralfkiaer, Charlotte M. Bonefeld, Mariusz A. Wasik, Thorbjørn Krejsgaard, Carsten Geisler, Elisabeth Ralfkiaer, Robert Gniadecki, Anders Woetmann, Niels Odum*

*Corresponding author af dette arbejde

    Publikation: Bidrag til tidsskriftArtikelForskningpeer review

    Abstrakt

    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.

    OriginalsprogEngelsk
    Sider (fra-til)5277-5286
    Antal sider10
    TidsskriftAnticancer Research
    Vol/bind34
    Udgave nummer10
    StatusUdgivet - 1 okt. 2014

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