PARP Inhibition Elicits STING-Dependent Antitumor Immunity in Brca1-Deficient Ovarian Cancer

Publication date: 11 December 2018Source: Cell Reports, Volume 25, Issue 11Author(s): Liya Ding, Hye-Jung Kim, Qiwei Wang, Michael Kearns, Tao Jiang, Carolynn E. Ohlson, Ben B. Li, Shaozhen Xie, Joyce F. Liu, Elizabeth H. Stover, Brooke E. Howitt, Roderick T. Bronson, Suzan Lazo, Thomas M. Roberts, Gordon J. Freeman, Panagiotis A. Konstantinopoulos, Ursula A. Matulonis, Jean J. ZhaoSummaryPARP inhibitors have shown promising clinical activities for patients with BRCA mutations and are changing the landscape of ovarian cancer treatment. However, the therapeutic mechanisms of action for PARP inhibition in the interaction of tumors with the tumor microenvironment and the host immune system remain unclear. We find that PARP inhibition by olaparib triggers robust local and systemic antitumor immunity involving both adaptive and innate immune responses through a STING-dependent antitumor immune response in mice bearing Brca1-deficient ovarian tumors. This effect is further augmented when olaparib is combined with PD-1 blockade. Our findings thus provide a molecular mechanism underlying antitumor activity by PARP inhibition and lay a foundation to improve therapeutic outcome for cancer patients.Graphical Abstract
Source: Cell Reports - Category: Cytology Source Type: research