Introduction Poly (adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis) are becoming the standard of care for epithelial ovarian cancer (EOC). Recently, clinical trials of triple maintenance therapy (PARPi+anti-angiogenic agent+anti-PD-1/L1) are actively ongoing. Here, we investigated the immunological effects of PARPi or triple maintenance therapy on T cells and their impact on clinical responses.
Methods We collected serial blood from EOC patients receiving PARPi therapy (cohort 1: PARPi, n=49; cohort 2: olaparib+bevacizumab+pembrolizumab, n=31). Peripheral T cells were analyzed using flow cytometry and compared according to the PARPi response. Progression-free survival (PFS) was assessed according to predictive biomarkers identified in a comparative analysis
Results Regulatory T cells (Tregs) were suppressed by PARPi therapy, whereas PD-1 was not significantly changed. Short PFS group exhibited a higher percentage of baseline PD-1+Tregs than long PFS group, and the patients with high percentage of PD-1+Tregs before treatment showed poor PFS in cohort 1. However, the expression of PD-1on Tregs significantly decreased after receiving triple maintenance therapy, and the reduction in PD-1+Tregs was associated with superior PFS in cohort 2 (P=0.0078).
Conclusion/Implications PARPi suppresses Tregs, but does not affect PD-1 expression. Addition of PD-1 blockade to PARPi decreases PD-1+Tregs, which have negative predictive value for PARPi monotherapy. Our data suggest that addition of PD-1 blockade to PARPi maintenance therapy is a promising option to improve survival outcomes for high-risk patients with ovarian cancer.
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