Poly (ADP-ribose) polymerase (
PARP) inhibitors have demonstrated great promise for treating
cancers with homologous recombination (HR) defects, such as germline BRCA1/2 mutation. Further studies suggest that
PARP inhibitors (PARPi) can also exhibit efficacy in HR-competent
cancers, by amplifying the DNA damage and inducing immunogenic cell death, and PARPi lead to increasing
tumor neoantigen, upregulation of
interferons and PD-L1, and modulation of the tumor microenvironment, which may facilitate a more profound antitumor immune response.
Immune checkpoint inhibitors (ICIs) targeting PD-1/PD-L1 or CTLA-4 have achieved impressive success in the treatment of different
malignancies. However, only a subset of populations derive clinical benefit, and the
biomarkers and resistance mechanisms are not fully understood. Therefore, given that PARPi could potentiate the
therapeutic effect of ICIs, PARPi combined with ICIs are becoming an alternative for patients who cannot benefit from ICI monotherapy. In this review, we focus on the mechanisms and immune role of PARPi and discuss the rationale and clinical studies of this combined regimen.