STING agonism reprograms tumor-associated macrophages and overcomes resistance to PARP inhibition in BRCA1-deficient models of breast cancer

oleh: 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

Format: Article
Diterbitkan: Nature Portfolio 2022-05-01

Deskripsi

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.