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

Cell Rep. 2018 Dec 11;25(11):2972-2980.e5. doi: 10.1016/j.celrep.2018.11.054.


PARP 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.

Keywords: BRCA deficiency; GEMM; PARP inhibition; PD-1 blockade; STING; immune response; immunotherapy; ovarian cancer; targeted therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BRCA1 Protein / deficiency*
  • BRCA1 Protein / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / metabolism
  • Female
  • HEK293 Cells
  • Humans
  • Immunity* / drug effects
  • Membrane Proteins / metabolism*
  • Mice, Inbred C57BL
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / immunology*
  • Ovarian Neoplasms / pathology
  • Phthalazines / pharmacology
  • Phthalazines / therapeutic use
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use*
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / metabolism
  • Treatment Outcome


  • BRCA1 Protein
  • Membrane Proteins
  • PDCD1 protein, human
  • Phthalazines
  • Piperazines
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Programmed Cell Death 1 Receptor
  • STING1 protein, human
  • olaparib