STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer
PARP inhibitor (PARPi) therapy has demonstrated only modest efficacy in advanced breast cancer with BRCA mutations. Here the authors show that, by suppressing PARPi-triggered DNA damage and reducing dsDNA production in BRCA1-deficient breast tumor cells, tumor associated macrophages contribute to PA...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-022-30568-1 |
| _version_ | 1811257012255719424 |
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| author | Qiwei Wang Johann S. Bergholz Liya Ding Ziying Lin Sheheryar K. Kabraji Melissa E. Hughes Xiadi He Shaozhen Xie Tao Jiang Weihua Wang Jason J. Zoeller Hye-Jung Kim Thomas M. Roberts Panagiotis A. Konstantinopoulos Ursula A. Matulonis Deborah A. Dillon Eric P. Winer Nancy U. Lin Jean J. Zhao |
| author_facet | Qiwei Wang Johann S. Bergholz Liya Ding Ziying Lin Sheheryar K. Kabraji Melissa E. Hughes Xiadi He Shaozhen Xie Tao Jiang Weihua Wang Jason J. Zoeller Hye-Jung Kim Thomas M. Roberts Panagiotis A. Konstantinopoulos Ursula A. Matulonis Deborah A. Dillon Eric P. Winer Nancy U. Lin Jean J. Zhao |
| author_sort | Qiwei Wang |
| collection | DOAJ |
| description | PARP inhibitor (PARPi) therapy has demonstrated only modest efficacy in advanced breast cancer with BRCA mutations. Here the authors show that, by suppressing PARPi-triggered DNA damage and reducing dsDNA production in BRCA1-deficient breast tumor cells, tumor associated macrophages contribute to PARPi resistance, that can be overcome by STING agonism. |
| first_indexed | 2024-04-12T17:50:54Z |
| format | Article |
| id | doaj.art-6187b06c5a3643429f9e40f41b6a7bb5 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-12T17:50:54Z |
| publishDate | 2022-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-6187b06c5a3643429f9e40f41b6a7bb52022-12-22T03:22:31ZengNature PortfolioNature Communications2041-17232022-05-0113111710.1038/s41467-022-30568-1STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancerQiwei Wang0Johann S. Bergholz1Liya Ding2Ziying Lin3Sheheryar K. Kabraji4Melissa E. Hughes5Xiadi He6Shaozhen Xie7Tao Jiang8Weihua Wang9Jason J. Zoeller10Hye-Jung Kim11Thomas M. Roberts12Panagiotis A. Konstantinopoulos13Ursula A. Matulonis14Deborah A. Dillon15Eric P. Winer16Nancy U. Lin17Jean J. Zhao18Department of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Cell Biology and Ludwig Center at Harvard, Harvard Medical SchoolDepartment of Cancer Immunology and Virology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Pathology, Brigham and Women’s HospitalDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Medical Oncology, Dana-Farber Cancer InstituteDepartment of Cancer Biology, Dana-Farber Cancer InstitutePARP inhibitor (PARPi) therapy has demonstrated only modest efficacy in advanced breast cancer with BRCA mutations. Here the authors show that, by suppressing PARPi-triggered DNA damage and reducing dsDNA production in BRCA1-deficient breast tumor cells, tumor associated macrophages contribute to PARPi resistance, that can be overcome by STING agonism.https://doi.org/10.1038/s41467-022-30568-1 |
| spellingShingle | Qiwei Wang Johann S. Bergholz Liya Ding Ziying Lin Sheheryar K. Kabraji Melissa E. Hughes Xiadi He Shaozhen Xie Tao Jiang Weihua Wang Jason J. Zoeller Hye-Jung Kim Thomas M. Roberts Panagiotis A. Konstantinopoulos Ursula A. Matulonis Deborah A. Dillon Eric P. Winer Nancy U. Lin Jean J. Zhao STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer Nature Communications |
| title | STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer |
| title_full | STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer |
| title_fullStr | STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer |
| title_full_unstemmed | STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer |
| title_short | STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer |
| title_sort | sting agonism reprograms tumor associated macrophages and overcomes resistance to parp inhibition in brca1 deficient models of breast cancer |
| url | https://doi.org/10.1038/s41467-022-30568-1 |
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