Nature Communications (May 2022)
STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer
- 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
Affiliations
- Qiwei Wang
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Johann S. Bergholz
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Liya Ding
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Ziying Lin
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Sheheryar K. Kabraji
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Melissa E. Hughes
- Department of Medical Oncology, Dana-Farber Cancer Institute
- Xiadi He
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Shaozhen Xie
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Tao Jiang
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Weihua Wang
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Jason J. Zoeller
- Department of Cell Biology and Ludwig Center at Harvard, Harvard Medical School
- Hye-Jung Kim
- Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute
- Thomas M. Roberts
- Department of Cancer Biology, Dana-Farber Cancer Institute
- Panagiotis A. Konstantinopoulos
- Department of Medical Oncology, Dana-Farber Cancer Institute
- Ursula A. Matulonis
- Department of Medical Oncology, Dana-Farber Cancer Institute
- Deborah A. Dillon
- Department of Pathology, Brigham and Women’s Hospital
- Eric P. Winer
- Department of Medical Oncology, Dana-Farber Cancer Institute
- Nancy U. Lin
- Department of Medical Oncology, Dana-Farber Cancer Institute
- Jean J. Zhao
- Department of Cancer Biology, Dana-Farber Cancer Institute
- DOI
- https://doi.org/10.1038/s41467-022-30568-1
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 17
Abstract
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.
