Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer
In recent years, tumor-infiltrating inflammatory cells within the tumor microenvironment have been extensively studied. However, much less is known about inflammatory cells in the normal tissue surrounding tumors. In this study, we assess the prognostic significance of tumor-associated macrophages (...
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2025-06-01
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| author | Marcel Hirschmann Sören Schnellhardt Matthias Rübner Sarah Segelhorst Oliver Ott Ramona Erber Christoph Daniel Maike Büttner-Herold Paul Gass Rainer Fietkau Luitpold Distel |
| author_facet | Marcel Hirschmann Sören Schnellhardt Matthias Rübner Sarah Segelhorst Oliver Ott Ramona Erber Christoph Daniel Maike Büttner-Herold Paul Gass Rainer Fietkau Luitpold Distel |
| author_sort | Marcel Hirschmann |
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| description | In recent years, tumor-infiltrating inflammatory cells within the tumor microenvironment have been extensively studied. However, much less is known about inflammatory cells in the normal tissue surrounding tumors. In this study, we assess the prognostic significance of tumor-associated macrophages (TAMs) in relation to disease-free survival (DFS) in patients with early-stage breast cancer. Our cohorts included patients from the APBI and BBCC trials, with eligible tumors being small in size and showing no signs of metastasis. We analyzed eight distinct inflammatory cell types in the normal tissue surrounding tumors, with a particular focus on the various macrophage subsets. There were clear differences in the frequencies of the different inflammatory cells, with a higher abundance of cells being found in the intraepithelial compartment compared to the stromal compartment. Notably, we found that M2-type macrophages located in the stromal compartment of tumor distant normal tissue exhibited a positive prognostic impact, in contrast to the M2-type macrophages found within the tumor itself. In the normal tissue surrounding tumors, there are surprisingly clear prognostic predictions for DFS. Normal tissue surrounding breast cancer tumors is clearly influenced by the tumor and could also influence the tumor in terms of growth and metastasis. Tumor-influenced inflammatory cells in the surrounding normal tissue could prevent the immune system from acting against the tumor and promote tumor growth through inflammation. |
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| issn | 2073-4409 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-20c9d699cd19467b96bd578bd263a42d2025-08-20T03:11:30ZengMDPI AGCells2073-44092025-06-01141182810.3390/cells14110828Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast CancerMarcel Hirschmann0Sören Schnellhardt1Matthias Rübner2Sarah Segelhorst3Oliver Ott4Ramona Erber5Christoph Daniel6Maike Büttner-Herold7Paul Gass8Rainer Fietkau9Luitpold Distel10Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Universitätsstraße 27, 91054 Erlangen, GermanyDepartment of Radiotherapy and Radiation Oncology, Saarland University Medical Center, 66421 Homburg, GermanyFrauenklinik, Comprehensive Cancer Center Erlangen-Europäische Metropolregion Nürnberg (EMN), Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Östliche Stadtmauerstraße 30, 91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Universitätsstraße 27, 91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Universitätsstraße 27, 91054 Erlangen, GermanyInstitute of Pathology, University Regensburg, Franz-Josef-Strauß-Allee 11, 93053 Regensburg, GermanyDepartment of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyDepartment of Nephropathology, Institute of Pathology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 91054 Erlangen, GermanyFrauenklinik, Comprehensive Cancer Center Erlangen-Europäische Metropolregion Nürnberg (EMN), Uniklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Östliche Stadtmauerstraße 30, 91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Universitätsstraße 27, 91054 Erlangen, GermanyDepartment of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), Universitätsstraße 27, 91054 Erlangen, GermanyIn recent years, tumor-infiltrating inflammatory cells within the tumor microenvironment have been extensively studied. However, much less is known about inflammatory cells in the normal tissue surrounding tumors. In this study, we assess the prognostic significance of tumor-associated macrophages (TAMs) in relation to disease-free survival (DFS) in patients with early-stage breast cancer. Our cohorts included patients from the APBI and BBCC trials, with eligible tumors being small in size and showing no signs of metastasis. We analyzed eight distinct inflammatory cell types in the normal tissue surrounding tumors, with a particular focus on the various macrophage subsets. There were clear differences in the frequencies of the different inflammatory cells, with a higher abundance of cells being found in the intraepithelial compartment compared to the stromal compartment. Notably, we found that M2-type macrophages located in the stromal compartment of tumor distant normal tissue exhibited a positive prognostic impact, in contrast to the M2-type macrophages found within the tumor itself. In the normal tissue surrounding tumors, there are surprisingly clear prognostic predictions for DFS. Normal tissue surrounding breast cancer tumors is clearly influenced by the tumor and could also influence the tumor in terms of growth and metastasis. Tumor-influenced inflammatory cells in the surrounding normal tissue could prevent the immune system from acting against the tumor and promote tumor growth through inflammation.https://www.mdpi.com/2073-4409/14/11/828early-stage breast cancernormal tissueM1M2macrophagestumor-infiltrating inflammatory cells |
| spellingShingle | Marcel Hirschmann Sören Schnellhardt Matthias Rübner Sarah Segelhorst Oliver Ott Ramona Erber Christoph Daniel Maike Büttner-Herold Paul Gass Rainer Fietkau Luitpold Distel Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer Cells early-stage breast cancer normal tissue M1 M2 macrophages tumor-infiltrating inflammatory cells |
| title | Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer |
| title_full | Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer |
| title_fullStr | Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer |
| title_full_unstemmed | Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer |
| title_short | Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer |
| title_sort | prognostic significance of macrophage phenotypes in peri tumoral normal tissue of early stage breast cancer |
| topic | early-stage breast cancer normal tissue M1 M2 macrophages tumor-infiltrating inflammatory cells |
| url | https://www.mdpi.com/2073-4409/14/11/828 |
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