@article{4828c6660fbe4cb78d3126528c0ad81d,
title = "PARPI triggers the STING-dependent immune response and enhances the therapeutic efficacy of immune checkpoint blockade independent of BRCANEss",
abstract = "PARP inhibitors (PARPi) have shown remarkable therapeu-way and stimulated production of type I IFNs to induce tic efficacy against BRCA1/2-mutant cancers through a syn-antitumor immunity independent of BRCAness. These effects thetic lethal interaction. PARPi exert their therapeutic effects of PARPi were further enhanced by immune checkpoint mainly through the blockade of ssDNA damage repair, which blockade. Overall, these results provide a mechanistic ratio-leads to the accumulation of toxic DNA double-strand breaks nale for using PARPi as immunomodulatory agents to harness specifically in cancer cells with DNA repair deficiency (BCRA-the therapeutic efficacy of immune checkpoint blockade. ness), including those harboring BRCA1/2 mutations. Here we show that PARPi-mediated modulation of the immune Significance: This work uncovers the mechanism behind response contributes to their therapeutic effects independently the clinical efficacy of PARPi in patients with both BRCA-of BRCA1/2 mutations. PARPi promoted accumulation of wild-type and BRCA-mutant tumors and provides a ratio-cytosolic DNA fragments because of unresolved DNA lesions, nale for combining PARPi with immunotherapy in patients which in turn activated the DNA-sensing cGAS–STING path-with cancer.",
author = "Jianfeng Shen and Wei Zhao and Zhenlin Ju and Lulu Wang and Yang Peng and Marilyne Labrie and Yap, {Timothy A.} and Mills, {Gordon B.} and Guang Peng",
note = "Funding Information: This research was supported by NCI Cancer Center Support Grant CA016672 to The University of Texas MD Anderson Cancer Center, Department of Defense grant OC140431and NIH R01 grant CA181663 to G. Peng, Cancer Prevention and Research Institute of Texas grant RP160242 to G. Peng and X. Shen, and the Adelson Medical Research Foundation and Cancer Prevention and Research Institute of Texas grant RP 170640 to G. Mills. Funding Information: T.A. Yap reports receiving other commercial research support from Astra-Zeneca, Bayer, Pfizer, Tesaro, Jounce, Eli Lilly, Seattle Genetics, Kyowa, Constellation, and Vertex Pharmceuticals, has received speakers bureau honoraria from AstraZeneca, Merck, Pfizer, and Tesaro, and is a consultant/advisory board member for Aduro, Almac, Ignyta, Jansen, Merck, Pfizer, Roche, Seattle Genetics, Vertex Pharmaceuticals, AstraZeneca, Atrin, Bayer, Bristol-Meyers Squibb, Calithera, Clovis, Cybrexa, and EMD Serono. G.B. Mills reports receiving commercial research grant from Ovarian Cancer Research Foundation, Adelson Medical Research Foundation, NanoString Technologies, Susan G. Komen Breast Cancer Foundation, Breast Cancer Research Foundation, Karus Therapeutics Ltd., AstraZeneca, Ionis, Pfizer Pharmaceuticals (including the current research), ImmunoMet, and Tesaro, Inc, other commercial research support from Prospect Creek Foundation and Takeda/Millienium Pharmaceuticals, has ownership interest (including stock, patents, etc.) in Catena Pharmaceuticals, ImmunoMet, SignalChem, Spindletop Ventures, and Tarveda, and is a consultant/advisory board member for AstraZeneca, Catena Pharmaceuticals, Tesaro, Critical Outcome Technologies, ImmunoMET, Ionis, Signalchem Lifesciences, Symphogen, Takeda/Millenium Pharmaceuticals, Tarveda, and Nuevolution. G. Peng received sponsored research funding from Pfizer (including the current research). No potential conflicts of interest were disclosed by the other authors. Publisher Copyright: {\textcopyright} 2018 American Association for Cancer Research.",
year = "2019",
month = jan,
day = "15",
doi = "10.1158/0008-5472.CAN-18-1003",
language = "English (US)",
volume = "79",
pages = "311--319",
journal = "Cancer Research",
issn = "0008-5472",
number = "2",
}