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Open AccessArticle

M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis

1
Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany
2
Department of Obstetrics and Gynecology, Heidelberg University Hospital, Ruprecht-Karls-University of Heidelberg, Im Neuenheimer Feld 440, 69120 Heidelberg, Germany
3
Institute of Pathology, Faculty of Medicine, LMU Munich, Thalkirchner Straße 36, 80337 Munich, Germany
4
Department of Medicine III, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, Germany
5
Department of Obstretrics and Gynecology, University Hospital Augsburg, Stenglinstraße 2, 86156 Augsburg, Germany
*
Author to whom correspondence should be addressed.
Cells 2020, 9(5), 1224; https://doi.org/10.3390/cells9051224
Received: 29 February 2020 / Revised: 6 May 2020 / Accepted: 12 May 2020 / Published: 15 May 2020
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Ovarian Cancer)
Multi drug resistance protein 1 (MDR1) expression on tumor cells has been widely investigated in context of drug resistance. However, the role of MDR1 on the immune cell infiltrate of solid tumors remains unknown. The aim of this study was to analyze the prognostic significance of a MDR1+ immune cell infiltrate in epithelial ovarian cancer (EOC) and to identify the MDR1+ leucocyte subpopulation. MDR1 expression was analyzed by immunohistochemistry in 156 EOC samples. In addition to MDR1+ cancer cells, we detected a MDR1+ leucocyte infiltrate (high infiltrate >4 leucocytes per field of view). Correlations and survival analyses were calculated. To identify immune cell subpopulations immunofluorescence double staining was performed. The MDR1+ leucocyte infiltrate was associated with human epidermal growth factor receptor 2 (HER2) (cc = 0.258, p = 0.005) and tumor-associated mucin 1 (TA-MUC1) (cc = 0.202, p = 0.022) expression on cancer cells. A high MDR1+ leucocyte infiltrate was associated with impaired survival, especially in patients whose carcinoma showed either serous histology (median OS 28.80 vs. 50.64 months, p = 0.027, n = 91) or TA-MUC1 expression (median OS 30.60 vs. 63.36 months, p = 0.015, n = 110). Similar findings for PFS suggest an influence of MDR1+ immune cells on the development of chemoresistance. A Cox regression analysis confirmed the independency of a high MDR1+ leucocyte infiltrate as prognostic factor. M2 macrophages were identified as main part of the MDR1+ leucocyte infiltrate expressing MDR1 as well as the M2 marker CD163 and the pan-macrophage marker CD68. Infiltration of MDR1+ leucocytes, mostly M2 macrophages, is associated with poor prognosis of EOC patients. Further understanding of the interaction of M2 macrophages, MDR1 and TA-MUC1 appears to be a key aspect to overcome chemoresistance in ovarian cancer. View Full-Text
Keywords: MDR1; M2 Macrophages; ovarian cancer; TA-MUC1; prognosis MDR1; M2 Macrophages; ovarian cancer; TA-MUC1; prognosis
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Badmann, S.; Heublein, S.; Mayr, D.; Reischer, A.; Liao, Y.; Kolben, T.; Beyer, S.; Hester, A.; Zeder-Goess, C.; Burges, A.; Mahner, S.; Jeschke, U.; Trillsch, F.; Czogalla, B. M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis. Cells 2020, 9, 1224.

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