Apatinib combined with an anti-PD-1 agent promotes antitumour immunity in mice with ovarian cancer

Abstract

Objective Apatinib is a noval antiangiogenic agents, and it has great clinical benefit. Immunotherapy has a low response rate in patients with ovarian cancer, but combination with antiangiogenic therapy might improve the antitumour response. The aim of our study was to assess the expression of programmed cell death 1 ligand 1 (PD-L1) in vivo and in vitro and the potential effect of apatinib in combination with an anti-PD-1 antibody in mice with ovarian cancer. Methods We assessed the expression of PD-L1 in vivo and in vitro by real-time quantitative reverse transcription–polymerase chain reaction (qRT‒PCR), flow cytometry and western blotting in different concentrations. We constructed a xenograft model and measured mouse weight and tumour size after treatment. Tumour tissues from the mice were subjected to HE staining, and we detected Ki-67, CD4 and CD8 expression by immunohistochemical staining (IHC). Results Apatinib monotherapy increased the expression of PD-L1 by dose-dependent, as determined by qRT‒PCR, flow cytometry, and western blotting in vivo and in vitro. Apatinib combined with an anti-PD-1 antibody had the most pronounced antitumour effect on ovarian cancer among the combination treatment and the two monotherapies. The most obvious changes were a decrease in Ki-67 expression and increases in CD4 and CD8 expression. Conclusions Our study showed that apatinib upregulates the expression of PD-L1 to exert antitumour effects. Apatinib in combination with an anti-PD-1 antibody led to a remarkable reduction in tumour growth, providing evidence for clinical trials.