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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MDPI AG
2020-05-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/5/1224 |
| _version_ | 1827716833640185856 |
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| author | Susann Badmann Sabine Heublein Doris Mayr Anna Reischer Yue Liao Thomas Kolben Susanne Beyer Anna Hester Christine Zeder-Goess Alexander Burges Sven Mahner Udo Jeschke Fabian Trillsch Bastian Czogalla |
| author_facet | Susann Badmann Sabine Heublein Doris Mayr Anna Reischer Yue Liao Thomas Kolben Susanne Beyer Anna Hester Christine Zeder-Goess Alexander Burges Sven Mahner Udo Jeschke Fabian Trillsch Bastian Czogalla |
| author_sort | Susann Badmann |
| collection | DOAJ |
| 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, <i>p</i> = 0.005) and tumor-associated mucin 1 (TA-MUC1) (cc = 0.202, <i>p</i> = 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, <i>p</i> = 0.027, n = 91) or TA-MUC1 expression (median OS 30.60 vs. 63.36 months, <i>p</i> = 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. |
| first_indexed | 2024-03-10T19:48:23Z |
| format | Article |
| id | doaj.art-1faef99a4309448b9fbe469943d3324c |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:48:23Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-1faef99a4309448b9fbe469943d3324c2023-11-20T00:34:17ZengMDPI AGCells2073-44092020-05-0195122410.3390/cells9051224M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor PrognosisSusann Badmann0Sabine Heublein1Doris Mayr2Anna Reischer3Yue Liao4Thomas Kolben5Susanne Beyer6Anna Hester7Christine Zeder-Goess8Alexander Burges9Sven Mahner10Udo Jeschke11Fabian Trillsch12Bastian Czogalla13Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyInstitute of Pathology, Faculty of Medicine, LMU Munich, Thalkirchner Straße 36, 80337 Munich, GermanyDepartment of Medicine III, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyDepartment of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistraße 15, 81377 Munich, GermanyMulti 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, <i>p</i> = 0.005) and tumor-associated mucin 1 (TA-MUC1) (cc = 0.202, <i>p</i> = 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, <i>p</i> = 0.027, n = 91) or TA-MUC1 expression (median OS 30.60 vs. 63.36 months, <i>p</i> = 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.https://www.mdpi.com/2073-4409/9/5/1224MDR1M2 Macrophagesovarian cancerTA-MUC1prognosis |
| spellingShingle | Susann Badmann Sabine Heublein Doris Mayr Anna Reischer Yue Liao Thomas Kolben Susanne Beyer Anna Hester Christine Zeder-Goess Alexander Burges Sven Mahner Udo Jeschke Fabian Trillsch Bastian Czogalla M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis Cells MDR1 M2 Macrophages ovarian cancer TA-MUC1 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 | MDR1 M2 Macrophages ovarian cancer TA-MUC1 prognosis |
| url | https://www.mdpi.com/2073-4409/9/5/1224 |
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