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Failure recovery of circulating NKG2D⁺CD56^dimNK cells in HBV-associated hepatocellular carcinoma after hepatectomy predicts early recurrence.

ABSTRACT: Dysfunction of natural killer (NK) cells has been implicated in the failure of antitumor immune responses in hepatocellular carcinoma (HCC) patients. However, the changes of NK profile in peripheral blood after surgery and tumor tissues of HCC patients, as well as the underlying reason and the significance are vague. Here, we observed that the frequencies of circulating NKG2D⁺CD56^dimNK cells decreased significantly in HBV-related HCC and were negatively correlated with the levels of serum TGF-? and soluble MICA (sMICA). In vitro experiments confirmed that the TGF-? and sMICA in tumor tissue homogenates, as well as sMICA in HCC cells culture supernatants could reduce the frequency of NKG2D⁺CD56^dimNK cells. In addition, in HCC patients the lower frequency of circulating NKG2D⁺CD56^dimNK cells was associated with larger tumor size and/or higher serum GGT. Noticeably, the frequency of NKG2D⁺CD56^dimNK cells at one month after surgery usually failed to restore in early recurrent patients, and that frequency was negatively associated with early recurrence and shorter overall survival. These results suggest that declined frequency of NKG2D⁺CD56^dimNK cells in HCC was associated with higher TGF-? and sMICA production, and low frequency of circulating NKG2D⁺CD56^dimNK cells at one month after surgery may predict poor prognosis of HBV-related HCC patients accepting hepatectomy.

SUBMITTER: Gao J

PROVIDER: S-EPMC4760296 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Failure recovery of circulating NKG2D+CD56dimNK cells in HBV-associated hepatocellular carcinoma after hepatectomy predicts early recurrence.

Gao Jian J Duan Zhaojun Z Zhang Ling L Huang Xiangbo X Long Lu L Tu Jing J Liang Hua H Zhang Yu Y Shen Tao T Lu Fengmin F

Oncoimmunology 20150707 1

Dysfunction of natural killer (NK) cells has been implicated in the failure of antitumor immune responses in hepatocellular carcinoma (HCC) patients. However, the changes of NK profile in peripheral blood after surgery and tumor tissues of HCC patients, as well as the underlying reason and the significance are vague. Here, we observed that the frequencies of circulating NKG2D+CD56dimNK cells decreased significantly in HBV-related HCC and were negatively correlated with the ...[more]

PMID: 26942056

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Project description:BackgroundSystemic lupus erythematosus (SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. Natural killer (NK) cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect alterations of peripheral NK cells and explore intrinsic mechanisms involving in NK cell abnormality in SLE.MethodsBlood samples from healthy controls (HCs) and patients with SLE and rheumatoid arthritis (RA) were collected. The NK count, NK subsets (CD56bright, CD56dimCD57-, and CD56dimCD57+), phenotypes, and apoptosis were evaluated with flow cytometer. Mitochondrial reactive oxygen species (mtROS) and total ROS levels were detected with MitoSOX Red and DCFH-DA staining respectively. Published data (GSE63829 and GSE23695) from Gene Expression Omnibus (GEO) was analyzed by Gene Set Enrichment Analysis (GSEA).ResultsTotal peripheral NK count was down-regulated in untreated SLE patients in comparison to that in untreated RA patients and HCs. SLE patients exhibited a selective reduction in peripheral CD56dimCD57+ NK cell proportion, which was negatively associated with disease activity and positively correlated with levels of complement(C)3 and C4. Compared with HCs, peripheral CD56dimCD57+ NK cells from SLE patients exhibited altered phenotypes, increased endogenous apoptosis and higher levels of mtROS and ROS. In addition, when treated with hydrogen peroxide (H2O2), peripheral CD56dimCD57+ NK cell subset was more prone to undergo apoptosis than CD56dimCD57- NK cells. Furthermore, this NK cell subset from SLE patients exhibited impaired cytotoxicity in response to activated CD4+ T cells in vitro.ConclusionOur study demonstrated a selective loss of mature CD56dimCD57+ NK cell subset in SLE patients, which may caused by preferential apoptosis of this subset under increased oxidative stress in SLE. The attenuated in vitro cytotoxicity of CD56dimCD57+ NK cells may contribute to the impaired ability of eliminating pathogenic CD4+ T cells in SLE.

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Failure recovery of circulating NKG2D⁺CD56^dimNK cells in HBV-associated hepatocellular carcinoma after hepatectomy predicts early recurrence.

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Failure recovery of circulating NKG2D<sup>+</sup>CD56<sup>dim</sup>NK cells in HBV-associated hepatocellular carcinoma after hepatectomy predicts early recurrence.

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