Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO

Li, Tuanjie; Yang, Yang; Hua, Xuefeng; Wang, Guoying; Liu, Wei; Jia, Changchang; Tai, Yan; Zhang, Qi; Chen, Guihua

doi:10.1016/j.canlet.2011.12.020

Cited by 271 publications

(215 citation statements)

References 35 publications

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“…116 Similar studies have also reported that HCCassociated fibroblasts trigger NK cell dysfunction via PGE2 and IDO. 73 Studies on the roles of fibroblast growth factor-2 in HCC development have indicated that fibroblast growth factor-2 levels in patients with liver cirrhosis or HCC were significantly higher than in healthy controls. Fibroblast growth factor-2 stimulation increased the expression of the MICA and decreased the expression of HLA class I molecules on HCC cells, resulting in enhanced NK sensitivity against HCC cells.…”

Section: Nkr Expression By Inhibitory Cytokinesmentioning

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: Nkr Expression By Inhibitory Cytokinesmentioning

confidence: 99%

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

et al. 2014

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“…In agreement with this study, fibroblasts derived from hepatocellular carcinoma patients induced deactivation of human NK cells, characterized by low expression of cytotoxic molecules and surface markers for cell activation, impaired production of cytokines, and decreased cytotoxic activity in vitro with a leukaemia cell line. These effects were partially mediated by CAF-derived PGE2 and indoleamine 2,3-dioxygenase (IDO) [75]. While these observations are intriguing, in vivo studies are required to confirm that CAFs can indeed function to suppress NK cytotoxic effector activity and thereby contribute to immune escape and foster tumour progression.…”

Section: Cafs Modulate Recruitment and Activation Of Lymphocytesmentioning

confidence: 99%

From sentinel cells to inflammatory culprits: cancer‐associated fibroblasts in tumour‐related inflammation

Servais

Erez

2012

The Journal of Pathology

133

113

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“…The effector function of CD8 + T cells is prone to be impaired by increased Tregs, which predicts a poor prognosis of HCC patients [10] . In addition, the functional impairment of other cells like natural killer (NK) cells also contributes to tumor progression [11] .…”

Section: Of Hccmentioning

confidence: 99%

Immunotherapy for hepatocellular carcinoma: From basic research to clinical use

Hong

Prasoon

et al. 2015

WJH

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Hepatocellular carcinoma (HCC) is a common cancer worldwide with a poor prognosis. Few strategies have been proven efficient in HCC treatment, particularly for those patients not indicated for curative resection or transplantation. Immunotherapy has been developed for decades for cancer control and is attaining more attention as a result of encouraging outcomes of new strategies such as chimeric antigen receptor T cells and immune checkpoint blockade. Right at the front of the new era of immunotherapy, we review the immunotherapy in HCC treatment, from basic research to clinical trials, covering anything from immunomodulators, tumor vaccines and adoptive immunotherapy. The mechanisms, efficacy and safety as well as the approach particulars are unveiled to assist readers to gain a concise but extensive understanding of immunotherapy of HCC.

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Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO

Cited by 271 publications

References 35 publications

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

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

From sentinel cells to inflammatory culprits: cancer‐associated fibroblasts in tumour‐related inflammation

Immunotherapy for hepatocellular carcinoma: From basic research to clinical use

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