Fredholm, Simon Mayland4; Gjerdrum, Lise Mette5; Willerslev-Olsen, Andreas6; Petersen, David Leander6; Nielsen, Dora Inger7; Kauczok, Claudia-S8; Wobser, Marion8; Ralfkiær, Ulrik9; Bonefeld, Charlotte M10; Wasik, Mariusz A11; Krejsgaard, Thorbjørn10; Geisler, Carsten10; Ralfkiaer, Elisabeth1; Gniadecki, Robert3; Woetmann, Anders10; Odum, Niels10
1 Patologiafdelingen, Diagnostisk Center, Rigshospitalet, The Capital Region of Denmark2 Hæmatologisk Klinik, Finsencentret, Rigshospitalet, The Capital Region of Denmark3 Dermato-Venerologisk Afdeling og Videncenter for Sårheling (D/S), Bispebjerg and Frederiksberg Hospital, The Capital Region of Denmark4 National Institute of Aquatic Resources5 Department of Pathology, Amager and Hvidovre Hospital, The Capital Region of Denmark6 Institut for International Sundhed, Immunologi og7 Risø National Laboratory for Sustainable Energy8 Tumor Biology Research Institute (Tumorbiologisches Forschungslabor), Würzburg, Germany.9 Dermatology and Allergy, Herlev and Gentofte Hospital, The Capital Region of Denmark10 University of Copenhagen11 University of Pennsylvania
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.
Anticancer Research, 2014, Vol 34, Issue 10, p. 5277-86