Peritumoural neutrophils negatively regulate adaptive immunity via the PD-L1/PD-1 signalling pathway in hepatocellular carcinoma

Background: pd-l1 expression on neutrophils contributes to the impaired immune response in infectious disease,but the detailed role of pd-l1 expression on neutrophils in hcc remains unclear. methods: we investigated the phenotype and morphology of neutrophils infiltrated in tumour tissues from both patients with hcc and hepatoma-bearing mice. results: we found that neutrophils dominantly infiltrated in the peritumoural region. the neutrophil-to-t cell ratio (nlr) was higher in peritumoural tissue than that in the intratumoural tissue and was negatively correlated with the overall survival of patients with hcc. infiltrating neutrophils displayed a phenotype of higher frequency of programmed cell death ligand 1 (pd-l1) positive neutrophils. the ratio of pd-l1+ neutrophils-to-pd-1+ t cells was higher in peritumoural tissue and better predicted the disease-free survival of patients with hcc. we further confirmed a higher frequency of pd-l1+ neutrophils and pd-1+ t cells in hepatoma-bearing mice. functionally,the pd-l1+ neutrophils from patients with hcc effectively suppressed the proliferation and activation of t cells,which could be partially reversed by the blockade of pd-l1. conclusions: our results indicate that the tumour microenvironment induces impaired antitumour immunity via the modulation of pd-l1 expression on tumour infiltrating neutrophils. © 2015 he et al.