Liver-infiltrating CD11b−CD27− NK subsets account for NK-cell dysfunction in patients with hepatocellular carcinoma and are associated with tumor progression  

作　　者：Qiong-Fang Zhang Wen-Wei Yin Yang Xia Ya-Yang Yi Qiu-Feng He Xing Wang Hong Ren Da-Zhi Zhang 

机构地区：[1]Key Laboratory of Molecular Biology for Infectious Diseases(Ministry of Education),Institute for Viral Hepatitis,Department of Infectious Diseases,The Second Affiliated Hospital,Chongqing Medical University,Chongqing 400016,PR China [2]Department of Urinary Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,PR China [3]Department of Hepatobiliary Surgery,The First Affiliated Hospital of Chongqing Medical University,Chongqing 400016,PR China [4]Department of Orthopaedics Surgery,The Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,PR China

出　　处：《Cellular & Molecular Immunology》2017年第10期819-829,共11页中国免疫学杂志（英文版）

基　　金：the National Natural Science Foundation of China(81171560,30930082,81171561 and 30972584);the National Science and Technology Major Project of China(2008ZX10002-006,2012ZX1002007001,2011ZX09302005,2012ZX09303001-001 and 2012ZX10002003);the National High Technology Research and Development Program of China(2011AA020111);the Key Project of the Chongqing Science and Technology Commission(cstc2012ggyyjsB10007);the Chongqing Natural Science Foundation(cstc2011jjA10025);the Medical Research Fund of the Chongqing Municipal Health Bureau(2009-1-71).

摘　　要：Natural killer(NK)cells have a vital role in killing hepatocellular carcinoma(HCC)cells;however,the mechanism underlying tumor-infiltrating NK(TINK)-cell dysfunction remains poorly understood.Using flow cytometry staining,we precisely characterized the frequency,phenotype and function of NK subsets distinguished by CD27 and CD11b in 30 patients with HCC in comparison to 30 healthy controls.Interestingly,we found a substantial proportion of liver-infiltrating CD11b−CD27−(DN)NK subsets in tumor tissue from HCC patients.Remarkably,these relatively expanded DN NK subsets exhibited an inactive and immature phenotype.By detecting the expression of CD107a and interferon-gamma(IFN-γ)on NK subsets and NK cells,we demonstrated that DN NK subsets exhibited a poor cytotoxic capacity and deficient potential to produce IFN-γin comparison to the other three subsets,which contributed to the dysfunction of TINK cells in HCC patients.In addition,we found that the presence of DN NK cells was closely associated with the clinical outcomes of HCC patients,as the frequency of DN NK cells among TINK cells was positively correlated with tumor stage and size.A large percentage of DN NK cells among TINK cells was an independent prognostic factor for lower survival in the 60-month follow-up period.In conclusion,a substantial proportion of CD11b−CD27−NK subsets among TINK cells accounts for NK-cell dysfunction in patients with HCC and is associated with tumor progression.Our study may provide a novel therapeutic target for the treatment of patients with HCC.

关 键 词：CD11B CD27 DYSFUNCTION NK SUBSETS 

分 类 号：R73[医药卫生—肿瘤]