Memory NK cells: why do they reside in the liver?

Jiang, Xiaojun; Chen, Yonglin; Peng, Hui; Tian, Zhigang

doi:10.1038/cmi.2013.8

Cited by 24 publications

(22 citation statements)

References 72 publications

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“…52 Second, studies in mice have suggested that some NK cells may express the capacity of memory and that these are particularly enriched in liver. 53 Third, NK cells get activated during HBV and HCV infections, 54 and experimental models with transgenic HBV mice 55 or HCV plasmid infected hepatoma cell lines 56 have indicated that NK cell-produced cytokines like IFNγ and TNF can clear hepatocytes of infection.…”

Section: Evidence For a Role For Nk Cells In Virus-associated Tumentioning

confidence: 99%

NK Cells and Virus-Related Cancers

2014

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Natural killer (NK) cells become activated during viral infections and can play roles in such infections by attacking virus-infected cells or by regulating adaptive immune responses. Experimental models suggest that NK cells may also have the capacity to restrain virus-induced cancers. Here, we discuss the seven viruses linked to human cancers and the evidence of NK cell involvement in these systems.

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Section: Evidence For a Role For Nk Cells In Virus-associated Tumentioning

confidence: 99%

NK Cells and Virus-Related Cancers

2014

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“…13,14 These liver-residing NK cells exert unique phenotypic and functional characteristics, such as immunological memory, suggesting the critical role of NK cells in the liver. 15,16 However, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. Lower NK cell numbers are significantly associated with poor prognosis for liver cancer.…”

Section: Introductionmentioning

confidence: 99%

NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma

et al. 2014

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Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. There is a significant correlation between chronic hepatitis B virus (HBV) infection and hepatocarcinogenesis. As the first line of host defense against viral infections and tumors, natural killer (NK) cells express a large number of immune recognition receptors (NK receptors (NKRs)) to recognize ligands on hepatocytes, liver sinusoidal endothelial cells, stellate cells and Kupffer cells, which maintain the balance between immune response and immune tolerance of NK cells. Unfortunately, the percentage and absolute number of liver NK cells decrease significantly during the development and progression of HCC. The abnormal expression of NK cell receptors and dysfunction of liver NK cells contribute to the progression of chronic HBV infection and HCC and are significantly associated with poor prognosis for liver cancer. In this review, we focus on the role of NK cell receptors in anti-tumor immune responses in HCC, particularly HBV-related HCC. We discuss specifically how tumor cells evade attack from NK cells and how emerging understanding of NKRs may aid the development of novel treatments for HCC. Novel mono-and combination therapeutic strategies that target the NK cell receptor-ligand system may potentially lead to successful and effective immunotherapy in HCC. Keywords: activating receptor; hepatocellular carcinoma; inhibitory receptor; natural killer cell; natural killer receptor INTRODUCTION Hepatocellular carcinoma (HCC) is currently the third leading cause of cancer mortality and a common poor-prognosis malignancy due to postoperative recurrence and metastasis. 1 Common clinical risk factors for HCC include hepatitis B virus (HBV)/hepatitis C virus (HCV) infection, heavy alcohol intake, steatohepatitis and diabetes. 2 Approximately 50% of HCC cases worldwide can be attributed to chronic HBV infection (CHB) and almost 75% of HCC cases occur in developing countries where HBV is endemic. 3,4 According to statistics, older male patients who are infected with HBV genotype C or co-infected with HCV, have high levels of viral load and have been exposed to the aflatoxin, or older male patients who have a family history of HCC tend to have a high risk of developing HCC. [5][6][7] Accumulating clinical and epidemiological evidence shows a significant correlation between chronic HBV infection and hepatocarcinogenesis. However, the underlying mechanisms

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“…In the liver, hepatic immune cells directly participate in the control and elimination of potentially dangerous biological and chemical material [50]; thus, it is possible that the antigenic activation of NK cells occurs directly in that organ [48, 51]. Indeed, bacterial products, toxins, and nutritional antigens have to be quickly eliminated by innate immune cells, before these dangerous substances could create damage at systemic level [50].…”

Section: First Evidences Of Nk Adaptive Featuresmentioning

confidence: 99%

“…Both HCMV and MCMV memory-like NK cells are not organ-specific, while in CHS model and in some viral infection memory-like NK cells are resident in the liver [46–48, 51, 72]. For this reason, it has been suggested that in CHS model the antigen recognition by NK cells could occur in the liver [48, 51]. On the other hand, the bone marrow is the primary site of long-lived NK cells generated after influenza infection [73].…”

Section: Concluding Remarks and Future Researchmentioning

confidence: 99%