title: High NKG2A expression contributes to NK cell exhaustion and predicts a poor prognosis of patients with liver cancer.
abstract: Background and Aims: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported.Methods: In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes.Results: The expression of NKG2A in NK cells and the NKG2A ligand, HLA-E, in intratumor HCC tissues was observed to be increased. These NK cells, and particularly CD56dimNK cells, with higher NKG2A expression showed features of functional exhaustion and were associated with a poor prognosis. The increase in NKG2A expression might be induced by IL-10, which was present at a high level in the plasma of HCC patients. Blocking IL-10 could specifically inhibit NKG2A expression in NK cells.Conclusions: These findings indicate that NKG2A expression is influenced by factors from cancer nests and contributes to NK cell exhaustion, suggesting that NKG2A blockade has the potential to restore immunity against liver tumors by reversing NK cell exhaustion.
authors.affiliation: Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Medical Science), School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Sun
authors.affiliation: Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China , Guangzhou, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University , Hefei, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Anhui Provincial Hospital Affiliated to Anhui Medical University , Hefei, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Huang
authors.affiliation: Xinjiang Key Laboratory of Echinococcosis, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University , Urumqi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wen
authors.affiliation: Xinjiang Key Laboratory of Echinococcosis, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical University , Urumqi, China.
authors.forename: Chuanshan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Medical Science), School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui, China.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Medical Science), School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui, China.
authors.forename: Jiaxi
authors.initials: J
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory, First Affiliated Hospital of Anhui Medical University , Hefei, China.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zheng
authors.affiliation: Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Medical Science), School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui, China.
authors.forename: Haoyu
authors.initials: H
authors.lastname: Sun
authors.affiliation: Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Medical Science), School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui, China.
authors.forename: Haiming
authors.initials: H
authors.lastname: Wei
authors.affiliation: Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Medical Science), School of Life Sciences and Medical Center, University of Science & Technology of China , Hefei, Anhui, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Medical Science), School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Sun
authors.affiliation: Institute of Immunology, The Key Laboratory of Innate Immunity and Chronic Disease (Chinese Academy of Medical Science), School of Life Sciences and Medical Center, University of Science & Technology of China, Hefei, Anhui, China; Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
keywords: HLA-E; Hepatocellular carcinoma; NK cells; NKG2A; prognosis