PARP inhibition and tumor immunity

Executive Summary: The goal of our current project is to identify the novel perspectives of PARPi in regulating tumor-induced immune suppression, and further explore a mechanism-driven combination immunocheckpoint blockade strategy to potentiate PARP inhibitor (PARPi). In particular, we will characterize the phenotype and function of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment, and explore the signaling pathways implicated by PARPi (ABT-888) in regulating myeloid cell differentiation and activation from BM-derived myeloid progenitors from tumor bearers using both gain-of-function and loss-of-function approaches. Finally, we will investigate the crosstalk between PARP inhibition and immune checkpoint, the PD-L1/PD-1 axis particularly in MDSCs, and further explore the therapeutic efficacy of PARPi in combination with anti-PD-1/PD-L1 therapy.