STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides

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

STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides

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

11 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Anticancer Research
Vol/bind	34
Udgave nummer	10
Sider (fra-til)	5277-5286
Antal sider	10
ISSN	0250-7005
Status	Udgivet - 1 okt. 2014

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Fredholm, S., Gjerdrum, L. M. R., Willerslev-Olsen, A., Petersen, D. L., Nielsen, I. Ø., Kauczok, C-S., Wobser, M., Ralfkiaer, U., Bonefeld, C. M., Wasik, M. A., Krejsgaard, T., Geisler, C., Ralfkiaer, E., Gniadecki, R., Andersen, A. W., & Odum, N. (2014). STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides. Anticancer Research, 34(10), 5277-5286.

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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.",

keywords = "Biopsy, Cell Line, Tumor, Eosinophils, Gene Knockout Techniques, HMGB1 Protein, Humans, Immunohistochemistry, Interleukin-5, Mycosis Fungoides, RNA Interference, STAT3 Transcription Factor, T-Lymphocytes",

author = "Simon Fredholm and Gjerdrum, {Lise Mette R} and Andreas Willerslev-Olsen and Petersen, {David L} and Nielsen, {Inger {\O}} and Claudia-S Kauczok and Marion Wobser and Ulrik Ralfkiaer and Bonefeld, {Charlotte M} and Wasik, {Mariusz A} and Thorbj{\o}rn Krejsgaard and Carsten Geisler and Elisabeth Ralfkiaer and Robert Gniadecki and Andersen, {Anders Woetmann} and Niels Odum",

year = "2014",

month = oct,

day = "1",

language = "English",

volume = "34",

pages = "5277--5286",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

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TY - JOUR

T1 - STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides

AU - Fredholm, Simon

AU - Gjerdrum, Lise Mette R

AU - Willerslev-Olsen, Andreas

AU - Petersen, David L

AU - Nielsen, Inger Ø

AU - Kauczok, Claudia-S

AU - Wobser, Marion

AU - Ralfkiaer, Ulrik

AU - Bonefeld, Charlotte M

AU - Wasik, Mariusz A

AU - Krejsgaard, Thorbjørn

AU - Geisler, Carsten

AU - Ralfkiaer, Elisabeth

AU - Gniadecki, Robert

AU - Andersen, Anders Woetmann

AU - Odum, Niels

PY - 2014/10/1

Y1 - 2014/10/1

N2 - 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.

AB - 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.

KW - Biopsy

KW - Cell Line, Tumor

KW - Eosinophils

KW - Gene Knockout Techniques

KW - HMGB1 Protein

KW - Humans

KW - Immunohistochemistry

KW - Interleukin-5

KW - Mycosis Fungoides

KW - RNA Interference

KW - STAT3 Transcription Factor

KW - T-Lymphocytes

M3 - Journal article

C2 - 25275020

SN - 0250-7005

VL - 34

SP - 5277

EP - 5286

JO - Anticancer Research

JF - Anticancer Research

IS - 10

ER -

STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides

Abstract

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