Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche
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| Veröffentlicht in: | Nature Communications vol. 16, no. 1 (2025), p. 1378 |
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| Veröffentlicht: |
Nature Publishing Group
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| Online-Zugang: | Citation/Abstract Full Text - PDF |
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| 022 | |a 2041-1723 | ||
| 024 | 7 | |a 10.1038/s41467-025-56347-2 |2 doi | |
| 035 | |a 3163630687 | ||
| 045 | 2 | |b d20250101 |b d20251231 | |
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| 245 | 1 | |a Brd7 loss reawakens dormant metastasis initiating cells in lung by forging an immunosuppressive niche | |
| 260 | |b Nature Publishing Group |c 2025 | ||
| 513 | |a Journal Article | ||
| 520 | 3 | |a Metastasis in cancer is influenced by epigenetic factors. Using an in vivo screen, we demonstrate that several subunits of the polybromo-associated BAF (PBAF) chromatin remodeling complex, particularly Brd7, are required for maintaining breast cancer metastatic dormancy in the lungs of female mice. Brd7 loss induces metastatic reawakening, along with modifications in epigenomic landscapes and upregulated oncogenic signaling. Breast cancer cells harboring Brd7 inactivation also reprogram the surrounding immune microenvironment by downregulating MHC-1 expression and promoting a pro-metastatic cytokine profile. Flow cytometric and single-cell analyses reveal increased levels of pro-tumorigenic inflammatory and transitional neutrophils, CD8+ exhausted T cells, and CD4+ stress response T cells in lungs from female mice harboring Brd7-deficient metastases. Finally, attenuating this immunosuppressive milieu by neutrophil depletion, neutrophil extracellular trap (NET) inhibition, or immune checkpoint therapy abrogates metastatic outgrowth. These findings implicate Brd7 and PBAF in triggering metastatic outgrowth in cancer, pointing to targetable underlying mechanisms involving specific immune cell compartments.Metastasis-initiating cells can reawaken from a dormant state that initially allowed them to survive, triggering metastatic outgrowth. Here, authors show that loss of Brd7 promotes an immunosuppressive tumor microenvironment that drives breast cancer metastatic reawakening from dormancy in the lung. | |
| 653 | |a Neutrophils | ||
| 653 | |a Metastasis | ||
| 653 | |a Lungs | ||
| 653 | |a Immune system | ||
| 653 | |a Breast cancer | ||
| 653 | |a Lymphocytes T | ||
| 653 | |a Lung cancer | ||
| 653 | |a Leukocytes (neutrophilic) | ||
| 653 | |a Immune checkpoint | ||
| 653 | |a Epigenetics | ||
| 653 | |a Females | ||
| 653 | |a Major histocompatibility complex | ||
| 653 | |a Tumor microenvironment | ||
| 653 | |a Chromatin remodeling | ||
| 653 | |a Dormancy | ||
| 653 | |a Flow cytometry | ||
| 653 | |a Metastases | ||
| 653 | |a Cellular stress response | ||
| 653 | |a CD4 antigen | ||
| 653 | |a CD8 antigen | ||
| 653 | |a Lymphocytes | ||
| 653 | |a Social | ||
| 773 | 0 | |t Nature Communications |g vol. 16, no. 1 (2025), p. 1378 | |
| 786 | 0 | |d ProQuest |t Health & Medical Collection | |
| 856 | 4 | 1 | |3 Citation/Abstract |u https://www.proquest.com/docview/3163630687/abstract/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |
| 856 | 4 | 0 | |3 Full Text - PDF |u https://www.proquest.com/docview/3163630687/fulltextPDF/embedded/L8HZQI7Z43R0LA5T?source=fedsrch |