期刊
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
卷 12, 期 -, 页码 -出版社
SAGE PUBLICATIONS LTD
DOI: 10.1177/1758835920944116
关键词
gynecologic cancer; immune-checkpoint inhibition; immune modulation; ovarian cancer; PARP inhibitor; PD-L1; STING
类别
Poly[adenosine diphosphate (ADP) ribose]polymerase (PARP) has multifaceted roles in the maintenance of genomic integrity, deoxyribonucleic acid (DNA) repair and replication, and the maintenance of immune-system homeostasis. PARP inhibitors are an attractive oncologic therapy, causing direct cancer cell cytotoxicity by propagating DNA damage and indirectly, by various mechanisms of immunostimulation, including activation of the cGAS/STING pathway, paracrine stimulation of dendritic cells, increased T-cell infiltration, and upregulation of death-ligand receptors to increase susceptibility to natural-killer-cell killing. However, these immunostimulatory effects are counterbalanced by PARPi-mediated upregulation of programmed cell-death-ligand 1 (PD-L1), which leads to immunosuppression. Combining PARP inhibition with immune-checkpoint blockade seeks to exploit the immune stimulatory effects of PARP inhibition while negating the immunosuppressive effects of PD-L1 upregulation.
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