title: Peritumoural neutrophils negatively regulate adaptive immunity via the PD-L1/PD-1 signalling pathway in hepatocellular carcinoma.
abstract: 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.
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, No.11 Xizhimen South Street, Beijing, 100044, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, 100044, China.
authors.forename: Gaixia
authors.initials: G
authors.lastname: He
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, No.11 Xizhimen South Street, Beijing, 100044, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, 100044, China.|Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Henghui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Henan Tumour Hospital, Zhengzhou, Henan, 450008, China.
authors.forename: Jinxue
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, No.11 Xizhimen South Street, Beijing, 100044, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, 100044, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China.
authors.forename: Yaxian
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, No.11 Xizhimen South Street, Beijing, 100044, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, 100044, China.
authors.forename: Xingwang
authors.initials: X
authors.lastname: Xie
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, No.11 Xizhimen South Street, Beijing, 100044, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, 100044, China.
authors.forename: Xueyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, No.11 Xizhimen South Street, Beijing, 100044, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, 100044, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Fei
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, No.11 Xizhimen South Street, Beijing, 100044, China.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, 100044, China.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Peking University People's Hospital, Peking University Hepatology Institute, No.11 Xizhimen South Street, Beijing, 100044, China. chenhongsong@pkuph.edu.cn.|Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing, 100044, China. chenhongsong@pkuph.edu.cn.
authors.forename: Hongsong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China. zenghui@ccmu.edu.cn.|Beijing Key Laboratory of Emerging Infectious Diseases, Beijing, 100015, China. zenghui@ccmu.edu.cn.
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D060890:B7-H1 Antigen / Q000235:genetics / Q000378:metabolism*; D015415:Biomarkers; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002452:Cell Count; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D051379:Mice; D009367:Neoplasm Staging; D020556:Neutrophil Infiltration / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
chemical_list: D060890:B7-H1 Antigen; D015415:Biomarkers; D061026:Programmed Cell Death 1 Receptor