title: STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides.
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.
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Simon
authors.initials: S
authors.lastname: Fredholm
authors.affiliation: Department of Pathology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Lise Mette R
authors.initials: LM
authors.lastname: Gjerdrum
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas
authors.initials: A
authors.lastname: Willerslev-Olsen
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: David L
authors.initials: DL
authors.lastname: Petersen
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Inger Ø
authors.initials: IØ
authors.lastname: Nielsen
authors.affiliation: Tumor Biology Research Institute (Tumorbiologisches Forschungslabor), Würzburg, Germany.
authors.forename: Claudia-S
authors.initials: CS
authors.lastname: Kauczok
authors.affiliation: Tumor Biology Research Institute (Tumorbiologisches Forschungslabor), Würzburg, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Wobser
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Ralfkiaer
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Bonefeld
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, U.S.A.
authors.forename: Mariusz A
authors.initials: MA
authors.lastname: Wasik
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thorbjørn
authors.initials: T
authors.lastname: Krejsgaard
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Carsten
authors.initials: C
authors.lastname: Geisler
authors.affiliation: Department of Pathology, Copenhagen University Hospital (Rigshospitalet), Copenhagen, Denmark.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Ralfkiaer
authors.affiliation: Department of Dermatology, Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Robert
authors.initials: R
authors.lastname: Gniadecki
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Woetmann
authors.affiliation: Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark ndum@sund.ku.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Odum
mesh_terms: D001706:Biopsy; D045744:Cell Line, Tumor; D004804:Eosinophils / Q000473:pathology*; D055786:Gene Knockout Techniques; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D009182:Mycosis Fungoides / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D034622:RNA Interference; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D024243:HMGB1 Protein; D015848:Interleukin-5; D050796:STAT3 Transcription Factor
keywords: CTCL; Cutaneous T-cell lymphoma; HMGB1; IL5; STAT3; eosinophils; high-mobility group protein B1; interleukin-5