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

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 cel...

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Autores principales: Badmann, Susann, Heublein, Sabine, Mayr, Doris, Reischer, Anna, Liao, Yue, Kolben, Thomas, Beyer, Susanne, Hester, Anna, Zeder-Goess, Christine, Burges, Alexander, Mahner, Sven, Jeschke, Udo, Trillsch, Fabian, Czogalla, Bastian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290705/
https://www.ncbi.nlm.nih.gov/pubmed/32429133
http://dx.doi.org/10.3390/cells9051224
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author Badmann, Susann
Heublein, Sabine
Mayr, Doris
Reischer, Anna
Liao, Yue
Kolben, Thomas
Beyer, Susanne
Hester, Anna
Zeder-Goess, Christine
Burges, Alexander
Mahner, Sven
Jeschke, Udo
Trillsch, Fabian
Czogalla, Bastian
author_facet Badmann, Susann
Heublein, Sabine
Mayr, Doris
Reischer, Anna
Liao, Yue
Kolben, Thomas
Beyer, Susanne
Hester, Anna
Zeder-Goess, Christine
Burges, Alexander
Mahner, Sven
Jeschke, Udo
Trillsch, Fabian
Czogalla, Bastian
author_sort Badmann, Susann
collection PubMed
description 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.
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spelling pubmed-72907052020-06-17 M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis Badmann, Susann Heublein, Sabine Mayr, Doris Reischer, Anna Liao, Yue Kolben, Thomas Beyer, Susanne Hester, Anna Zeder-Goess, Christine Burges, Alexander Mahner, Sven Jeschke, Udo Trillsch, Fabian Czogalla, Bastian Cells Article 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. MDPI 2020-05-15 /pmc/articles/PMC7290705/ /pubmed/32429133 http://dx.doi.org/10.3390/cells9051224 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Badmann, Susann
Heublein, Sabine
Mayr, Doris
Reischer, Anna
Liao, Yue
Kolben, Thomas
Beyer, Susanne
Hester, Anna
Zeder-Goess, Christine
Burges, Alexander
Mahner, Sven
Jeschke, Udo
Trillsch, Fabian
Czogalla, Bastian
M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis
title M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis
title_full M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis
title_fullStr M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis
title_full_unstemmed M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis
title_short M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis
title_sort m2 macrophages infiltrating epithelial ovarian cancer express mdr1: a feature that may account for the poor prognosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290705/
https://www.ncbi.nlm.nih.gov/pubmed/32429133
http://dx.doi.org/10.3390/cells9051224
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