Estrogen-induced immune changes within the normal mammary gland
Abstract Breast cancer (BCa) incidence increases following aberrant hormone exposure, which has been linked to direct effects on estrogen receptor (ER)+ mammary epithelium. While estrogen exposure during mammary involution has been shown to drive tumour growth via neutrophils, the potential for the...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-21871-4 |
| _version_ | 1817970213443862528 |
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| author | Helen Tower Genevieve Dall Ashleigh Davey Melanie Stewart Patrick Lanteri Meagan Ruppert Maria Lambouras Ibraheem Nasir Serene Yeow Phillip K. Darcy Wendy V. Ingman Belinda Parker Nicole M. Haynes Kara L. Britt |
| author_facet | Helen Tower Genevieve Dall Ashleigh Davey Melanie Stewart Patrick Lanteri Meagan Ruppert Maria Lambouras Ibraheem Nasir Serene Yeow Phillip K. Darcy Wendy V. Ingman Belinda Parker Nicole M. Haynes Kara L. Britt |
| author_sort | Helen Tower |
| collection | DOAJ |
| description | Abstract Breast cancer (BCa) incidence increases following aberrant hormone exposure, which has been linked to direct effects on estrogen receptor (ER)+ mammary epithelium. While estrogen exposure during mammary involution has been shown to drive tumour growth via neutrophils, the potential for the ER + immune microenvironment to mediate part (in addition to mammary epithelial cells) of hormonally controlled BCa risk during normal development has not been assessed. We collected mammary tissue, lymph nodes and blood from tumour naïve mice treated with, oophorectomy, estrogen (17β estradiol) or Fulvestrant. Flow cytometry was used to examine the impact on the frequency of innate and adaptive immune cells. Oophorectomy and fulvestrant decreased the proportion of macrophages, particularly pro-tumour polarized M2 macrophages and neutrophils. Conversely, dendritic cells were increased by these therapies, as were eosinophils. Estrogen increased the proportion of M2 macrophages and to a lesser extent CD4-CD8- double negative and FoxP3+ regulatory T cells but decreased CD8 + T cells and B cells. Excluding eosinophils, these changes were restricted to the mammary tissue. This suggests that inhibiting estrogen action lowers the immune suppressive myeloid cells, increases in antigen presentation and eosinophil-mediated direct or indirect cytotoxic effects. In contrast, estrogen exposure, which drives BCa risk, increases the suppressive myeloid cells and reduces anti-tumour cytotoxic T cells. The impact of hormonal exposure on BCa risk, may in part be linked to its immune modulatory activity. |
| first_indexed | 2024-04-13T20:32:14Z |
| format | Article |
| id | doaj.art-49ec8610163947a8b32e9c455e48f421 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T20:32:14Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-49ec8610163947a8b32e9c455e48f4212022-12-22T02:31:09ZengNature PortfolioScientific Reports2045-23222022-11-0112111410.1038/s41598-022-21871-4Estrogen-induced immune changes within the normal mammary glandHelen Tower0Genevieve Dall1Ashleigh Davey2Melanie Stewart3Patrick Lanteri4Meagan Ruppert5Maria Lambouras6Ibraheem Nasir7Serene Yeow8Phillip K. Darcy9Wendy V. Ingman10Belinda Parker11Nicole M. Haynes12Kara L. Britt13Breast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreSir Peter MacCallum Department of Oncology, The University of MelbourneDiscipline of Surgical Specialties, Adelaide Medical School, The Queen Elizabeth Hospital, University of AdelaideSir Peter MacCallum Department of Oncology, The University of MelbourneSir Peter MacCallum Department of Oncology, The University of MelbourneBreast Cancer Risk and Prevention Laboratory, Peter MacCallum Cancer CentreAbstract Breast cancer (BCa) incidence increases following aberrant hormone exposure, which has been linked to direct effects on estrogen receptor (ER)+ mammary epithelium. While estrogen exposure during mammary involution has been shown to drive tumour growth via neutrophils, the potential for the ER + immune microenvironment to mediate part (in addition to mammary epithelial cells) of hormonally controlled BCa risk during normal development has not been assessed. We collected mammary tissue, lymph nodes and blood from tumour naïve mice treated with, oophorectomy, estrogen (17β estradiol) or Fulvestrant. Flow cytometry was used to examine the impact on the frequency of innate and adaptive immune cells. Oophorectomy and fulvestrant decreased the proportion of macrophages, particularly pro-tumour polarized M2 macrophages and neutrophils. Conversely, dendritic cells were increased by these therapies, as were eosinophils. Estrogen increased the proportion of M2 macrophages and to a lesser extent CD4-CD8- double negative and FoxP3+ regulatory T cells but decreased CD8 + T cells and B cells. Excluding eosinophils, these changes were restricted to the mammary tissue. This suggests that inhibiting estrogen action lowers the immune suppressive myeloid cells, increases in antigen presentation and eosinophil-mediated direct or indirect cytotoxic effects. In contrast, estrogen exposure, which drives BCa risk, increases the suppressive myeloid cells and reduces anti-tumour cytotoxic T cells. The impact of hormonal exposure on BCa risk, may in part be linked to its immune modulatory activity.https://doi.org/10.1038/s41598-022-21871-4 |
| spellingShingle | Helen Tower Genevieve Dall Ashleigh Davey Melanie Stewart Patrick Lanteri Meagan Ruppert Maria Lambouras Ibraheem Nasir Serene Yeow Phillip K. Darcy Wendy V. Ingman Belinda Parker Nicole M. Haynes Kara L. Britt Estrogen-induced immune changes within the normal mammary gland Scientific Reports |
| title | Estrogen-induced immune changes within the normal mammary gland |
| title_full | Estrogen-induced immune changes within the normal mammary gland |
| title_fullStr | Estrogen-induced immune changes within the normal mammary gland |
| title_full_unstemmed | Estrogen-induced immune changes within the normal mammary gland |
| title_short | Estrogen-induced immune changes within the normal mammary gland |
| title_sort | estrogen induced immune changes within the normal mammary gland |
| url | https://doi.org/10.1038/s41598-022-21871-4 |
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