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

• Published in: Journal of experimental & clinical cancer research Vol. 34; no. 1; p. 141
• Main Authors: He, Gaixia, Zhang, Henghui, Zhou, Jinxue, Wang, Beibei, Chen, Yanhui, Kong, Yaxian, Xie, Xingwang, Wang, Xueyan, Fei, Ran, Wei, Lai, Chen, Hongsong, Zeng, Hui
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 18.11.2015; BioMed Central
• Subjects: Adaptive Immunity; Analysis; Animals; Apoptosis; B7-H1 Antigen - genetics; B7-H1 Antigen - metabolism; Biomarkers; Carcinoma, Hepatocellular - immunology; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - mortality; Carcinoma, Hepatocellular - pathology; Care and treatment; Cell Count; Cellular signal transduction; Complications and side effects; Disease Models, Animal; Female; Gene Expression; Gene Expression Regulation, Neoplastic; Hepatoma; Humans; Liver Neoplasms - immunology; Liver Neoplasms - metabolism; Liver Neoplasms - mortality; Liver Neoplasms - pathology; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Mice; Neoplasm Staging; Neutrophil Infiltration - immunology; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Neutrophils - pathology; Prognosis; Programmed Cell Death 1 Receptor - genetics; Programmed Cell Death 1 Receptor - metabolism; Signal Transduction; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology
• ISSN: 1756-9966; 0392-9078; 1756-9966
• DOI: 10.1186/s13046-015-0256-0

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. We investigated the phenotype and morphology of neutrophils infiltrated in tumour tissues from both patients with HCC and hepatoma-bearing mice. 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. Our results indicate that the tumour microenvironment induces impaired antitumour immunity via the modulation of PD-L1 expression on tumour infiltrating neutrophils.