Title |
Peritumoural neutrophils negatively regulate adaptive immunity via the PD-L1/PD-1 signalling pathway in hepatocellular carcinoma
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Published in |
Journal of Experimental & Clinical Cancer Research, November 2015
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DOI | 10.1186/s13046-015-0256-0 |
Pubmed ID | |
Authors |
Gaixia He, Henghui Zhang, Jinxue Zhou, Beibei Wang, Yanhui Chen, Yaxian Kong, Xingwang Xie, Xueyan Wang, Ran Fei, Lai Wei, Hongsong Chen, Hui Zeng |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Unknown | 2 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Spain | 1 | <1% |
Sweden | 1 | <1% |
Unknown | 124 | 98% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 25 | 20% |
Researcher | 16 | 13% |
Student > Bachelor | 15 | 12% |
Student > Master | 12 | 10% |
Student > Postgraduate | 8 | 6% |
Other | 19 | 15% |
Unknown | 31 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 23 | 18% |
Medicine and Dentistry | 22 | 17% |
Agricultural and Biological Sciences | 20 | 16% |
Immunology and Microbiology | 14 | 11% |
Chemistry | 2 | 2% |
Other | 5 | 4% |
Unknown | 40 | 32% |