Identification and Functional Analysis of Ligands for Natural Killer Cell Activating Receptors in Colon Carcinoma

Zhang, Zhang; Su, Tao; He, Liang; Wang, Hongtao; Ji, Gang; Liu, Xiaonan; Zhang, Yun; Dong, Guanglong

doi:10.1620/tjem.226.59

Cited by 33 publications

(25 citation statements)

References 45 publications

(54 reference statements)

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“…20,29,32,37,[41][42][43] NKG2D ligands are often upregulated on a wide range of tumor cells in response to cellular stress during malignant transformation. However, as tumors progress, soluble MICA/B or ULBPs are often shed from the membranes of tumor cells.…”

Section: Nk Receptors In Tumorsmentioning

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: Nk Receptors In Tumorsmentioning

confidence: 99%

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

et al. 2014

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“…Since the expression of MICA molecules is associated with stress-induced factors, their increased expression can be induced by viral or bacterial infection. MICA expression is observed in many epithelial cell-derived tumors such as colon cancer, breast cancer, and lung cancer (Vallian et al, 2012;Zhang et al, 2012;Chen et al, 2013), and on the surface of some melanoma cells. Renal cancer cells also express MICA (Qiu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Expression and clinical value of the soluble major histocompatibility complex class I-related chain A molecule in the serum of patients with renal tumors

Yk¹,

Cm²,

Gj³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. We investigated the expression and clinical value of the soluble major histocompatibility complex class I-related chain A (sMICA) molecule in the serum of patients with renal tumors. Sixty patients diagnosed with renal tumors were enrolled in the experimental group, whereas 20 healthy volunteers served as the control group. The sMICA levels were measured via enzyme-linked immunosorbent assay, and the results were analyzed in combination with data from pathology examination. The experimental group had a statistically significant higher sMICA level (P < 0.05) than the control group. The sMICA level was higher in patients with malignant tumors than in those with benign tumors. We also observed a positive relationship among different tumor-node-metastasis (TNM) pathological stages with more advanced 7234©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (2): 7233-7240 (2015) diseases exhibiting higher sMICA levels. As a tumor-associated antigen, MICA has a close relationship with renal tumorigenesis and immune escape. Our results indicated that sMICA levels were related to tumor pathology, TNM stage, and metastasis. Therefore, sMICA might be a potential marker for tumor characteristics, prognosis, and recurrence prediction.

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“…The importance of DNAM1 has been reported in breast cancer, CRC, AML, and melanoma [17,18,37,53] and in melanoma, it has been shown that tumor-associated ibroblasts (TAF) by modulating the surface expression of DNAM-1 based on cell-to-cell interactions could inhibit NK cell function [54]. Also, DNAM1 ligand CD155 upregulation on multiple myeloma (MM) cells has been reported and resulted in increased sensitivity to NK cell-mediated lysis [55].…”

Section: Stimulatory Nectin-binding Adhesion Moleculementioning

confidence: 99%

The Role of Activating and Inhibitory NK Cell Receptors in Antitumor Immune Response

Konjević¹,

Vuletić²,

Martinović³

et al. 2017

Natural Killer Cells

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Natural killer (NK) cells express many newly identiied activating and inhibitory receptors that upon engagement by cognate ligands on target tumor cells regulate NK cell antitumor activity. Recently, several paired NK cell receptor families that include receptors with similar binding speciicities but opposite function have been deined. The expression of most important activating receptors, natural killer group 2D (NKG2D), natural cytotoxic receptors (NCR), DNAX accessory molecule-1 (DNAM1) and activating killer cell immunoglobulin-like receptors (KAR) is often decreased, while the expression of most prominent inhibitory NK cell receptors, killer cell inhibitory immunoglobulin-like receptors (KIR) and CD94/NKG2A, may occasionally be increased in malignancies. These data indicate that impaired NK cell antitumor response results from NK cell receptor alterations induced by suppressive factors in the tumor microenvironment, including cytokines, growth factors, enzymes and metabolites, as well as by chronic NK cell receptor engagement by the tumor. The established alterations in NK cell receptor expression in cancer patients represent potential disease biomarkers and may aid in choosing therapies that upregulate activating or block inhibitory receptor function. Accumulating knowledge of NK cell biology has been helpful in creating novel therapeutic approaches that by release from tumor-inluenced immunosuppression potentiate NK cell activity in cancer patients.

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Identification and Functional Analysis of Ligands for Natural Killer Cell Activating Receptors in Colon Carcinoma

Cited by 33 publications

References 45 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

Expression and clinical value of the soluble major histocompatibility complex class I-related chain A molecule in the serum of patients with renal tumors

The Role of Activating and Inhibitory NK Cell Receptors in Antitumor Immune Response

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