NK cells in immunotolerant organs

Sun, Haoyu; Sun, Cheng; Tian, Zhigang; Xiao, Weihua

doi:10.1038/cmi.2013.9

Cited by 66 publications

(61 citation statements)

References 136 publications

(164 reference statements)

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“…12 More importantly, the percentage of NK cells in the liver is known to be nearly five times greater than the percentages in blood or spleen. 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.…”

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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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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“…In the lung, NK cells make up the highest percentage of resident lymphocytes compared with any other tissue (12,13), suggesting that quick and effective NKmediated immune responses are critical for eliminating pathogens and maintaining homeostasis in the lung. Indeed, activation of lung NK cells promotes adaptive immune function and the elimination of viruses during influenza virus infection.…”

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confidence: 99%

Klebsiella pneumoniaeAlleviates Influenza-Induced Acute Lung Injury via Limiting NK Cell Expansion

Wang

Sun

et al. 2014

The Journal of Immunology

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A protective effect induced by bacterial preinfection upon a subsequent lethal influenza virus infection has been observed, but the underlying immune mechanisms have not yet been fully elucidated. In this study, we used a mouse model of Klebsiella pneumoniae preinfection to gain insight into how bacterial preinfection influences the subsequent lethal influenza virus infection. We found that K. pneumoniae preinfection significantly attenuated lung immune injury and decreased mortality during influenza virus infection, but K. pneumoniae–specific immunity was not involved in this cross-protection against influenza virus. K. pneumoniae preinfection limited NK cell expansion, which was involved in influenza-induced immune injury and death. Furthermore, K. pneumoniae preinfection could not control NK cell expansion and death during influenza virus infection in Rag1−/− mice, but adoptive transfer of T cells from wild-type mice was able to restore this protective effect. Our data suggest that the adaptive immune response activated by bacterial infection limits the excessive innate immune response induced by a subsequent influenza infection, ultimately protecting mice from death.

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“…Their anti-tumor response is by direct lysis of malignant cells [101] . They express a number of immune receptors (NKRs) that are able to recognize ligands on hepatocytes, stellate cells and Kupffer cells to maintain proper immune function [103,104] . MHC class Ⅰ-related chain A (MICA) is a ligand for NK cell stimulatory receptor NKG2D and is expressed in HCC [105] .…”

Section: Natural Killer Cellsmentioning

confidence: 99%