Polymorphisms in Natural Killer Cell Receptor Protein 2D (NKG2D) as a Risk Factor for Cholangiocarcinoma

Wadsworth, Chris; Dixon, Peter H.; Taylor-Robinso, Simon D.; Kim, Jin U.; Zabron, Abigail; Wong, J; Chapman, Michael H.; McKay, Siobhan C.; Spalding, Duncan; Wasan, Harpreet; Pereira, Stephen P.; Thomas, Howard; Whittaker, John C.; Williamson, Catherine; Khan, Shahid A.

doi:10.1016/j.jceh.2018.06.521

Cited by 10 publications

(11 citation statements)

References 16 publications

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“…Both SNPs were not detected in the originally established HNK haplotype but appeared in LD with rs1049174 and rs2255336 in the Scandinavian individuals. A study conducted on non-PSC Caucasian patients failed to reveal any correlation between NKG2D genetic variation and CC development risk [82]. Regardless of the ethnic differences in the compared populations, the failure to reproduce the association may arise from different pathogeneses of sporadic CC and PSC-related CC.…”

Section: Cancers and Cancer Immunotherapymentioning

confidence: 98%

“…T allele frequency higher in South Indian rheumatoid arthritis patients with deformities-marker of severe disease [80] A allele associated with lower frequency of retinopathy-vascular complication in sickle cell disease in Sub-Saharan African and French West Indian patients [79] rs2617170 (T > C) KLRC4 exon 3 TT homozygosity associated with lower risk of recurrent miscarriage among North African women [81] rs7397310 (T > C) 3' flanking region of KLRK1 No association between alleles frequency and cholangiocarcinoma risk in Caucasian individuals [82] rs2900420 (G > A) 3' flanking region of KLRK1 A allele associated with better survival time in advanced-stage non-small cell lung cancer Non-Hispanic Whites patients treated with first-line chemotherapy [83] rs10772271 (G > A) 3' flanking region of KLRK1 A allele associated with decreased NKG2D expression on NK cells in Finnish infants, and increased viral bronchiolitis susceptibility [84] rs11053781 (G > A) KLRK1 intron 3 Higher G allele frequency in PSC Scandinavian patients with cholangiocarcinoma [85] rs7972757 (A > G) Intergenic KLRC4-KLRK1 Higher A allele frequency in placental malaria affected African patients [86] rs728010 (G > A) Intergenic KLRC4-KLRK1 Higher GG genotype frequency in placental malaria affected African patients [86] rs12821887 (T > C) Intergenic KLRC4-KLRK1 Higher TT genotype frequency in placental malaria affected African patients [86] rs2617167 (G > A) Intergenic KLRC4-KLRK1 Higher A allele frequency in PSC Scandinavian patients with cholangiocarcinoma [85] Table 2. Cont.…”

Section: Gg Genotype Associated With Inefficient Anti-tnf Therapy In Rheumatoid Arthritismentioning

confidence: 99%

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NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications

Siemaszko

Marzec-Przyszlak

Bogunia‐Kubik

2021

Cells

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Natural Killer (NK) cells are natural cytotoxic, effector cells of the innate immune system. They can recognize transformed or infected cells. NK cells are armed with a set of activating and inhibitory receptors which are able to bind to their ligands on target cells. The right balance between expression and activation of those receptors is fundamental for the proper functionality of NK cells. One of the best known activating receptors is NKG2D, a member of the CD94/NKG2 family. Due to a specific NKG2D binding with its eight different ligands, which are overexpressed in transformed, infected and stressed cells, NK cells are able to recognize and attack their targets. The NKG2D receptor has an enormous significance in various, autoimmune diseases, viral and bacterial infections as well as for transplantation outcomes and complications. This review focuses on the NKG2D receptor, the mechanism of its action, clinical relevance of its gene polymorphisms and a potential application in various clinical settings.

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Section: Cancers and Cancer Immunotherapymentioning

confidence: 98%

Section: Gg Genotype Associated With Inefficient Anti-tnf Therapy In Rheumatoid Arthritismentioning

confidence: 99%

NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications

Siemaszko

Marzec-Przyszlak

Bogunia‐Kubik

2021

Cells

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“…83 Polymorphism of natural killer group 2D (NKG2D), an NK cell receptor in primary sclerosing cholangitis patients, was a risk factor for cholangiocarcinoma. 84 Overexpression of NKG2D ligands predicted favorable prognosis. 85 Moreover, multiple alterations of genes that encode NK cell immunoglobulinlike receptors (KIR) were identified in BTC and associated with patient poor outcomes.…”

Section: Cellular Senescencementioning

confidence: 99%

“…Natural killer (NK) cells are innate lymphocytes that induce virally infected and neoplastic cells death by releasing cytotoxic molecules (perforin, granzymes, and IFN‐γ) 83 . Polymorphism of natural killer group 2D (NKG2D), an NK cell receptor in primary sclerosing cholangitis patients, was a risk factor for cholangiocarcinoma 84 . Overexpression of NKG2D ligands predicted favorable prognosis 85 .…”

Section: Molecular Mechanisms Underlying Aging‐mediated Btcmentioning

confidence: 99%

Aging and biliary tract cancers: Epidemiology, molecular biology, and clinical practice

et al. 2022

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Biliary tract cancer (BTC) that contains cholangiocarcinoma, gallbladder cancer, and ampullary cancer is highly malignant and mostly diagnosed in elderly patients. Over the past decades, human life has globally risen; thus, aging emerges as the primary risk factor for BTC. However, an effective treatment for this vulnerable population remains a large clinical challenge. As a result, the incidence and mortality of TBC remains high. Here, we discuss the potential link between aging and BTC from the aspects of molecular and cellular mechanisms, surgical resection, and chemotherapy. In addition, we update a number of clinical trials that are currently ongoing in elderly patients. The overview of BTC in elderly patients is expected to help develop a new therapeutic strategy tailored to this elderly population, ultimately improving their life quality.

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“…Regarding the innate immune system, Natural Killer (NK) cells are important components of tumor surveillance [56]. Epidemiological data suggest that polymorphisms of important genes related to NK cells functions (KIR and NKG2D) might be associated with the risk of developing CCA [57,58], suggesting an important role of these cells on the immune surveillance against CCA. Furthermore, the infiltration by NK cells has been associated with better survival in resected iCCA [59].…”

Section: Description Of the Tumor Immune Microenvironment In Ccamentioning

confidence: 99%

Targeting the tumor microenvironment in cholangiocarcinoma: implications for therapy

Louis

Edeline

Coulouarn

2021

Expert Opinion on Therapeutic Targets

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Introduction: Cholangiocarcinoma (CCA) is a rare but deadly cancer worldwide, mainly as a result of a late diagnosis and limited effective treatments. Targeting the tumor microenvironment (TME) emerged as a relevant strategy in CCA which is characterized by an abundant desmoplastic stroma. Areas covered:In this review, we describe the role of different compartments of the TME in CCA, focusing on the preclinical rationale for the development of innovative therapies. Relevant literature was identified by a PubMed search covering the last decade (2010)(2011)(2012)(2013)(2014)(2015)(2016)(2017)(2018)(2019)(2020).Expert opinion: Low efficacy of surgery and cytotoxic chemotherapy for a long term cure of patients with CCA emphasize the need for developing innovative therapeutic strategies and companion biomarkers. Single-cell RNA sequencing of the stroma is providing a critical functional characterization of TME in CCA and is paving the way for immunotherapies, as well as cancer-associated fibroblast and extracellular matrixoriented treatments. We believe that the development of treatments targeting different components the TME will produce the best results if thought as a combination with cytotoxic chemotherapy. Positive results would also be clearer if biomarkers are developed to define the population of interest for each combination strategy.

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Polymorphisms in Natural Killer Cell Receptor Protein 2D (NKG2D) as a Risk Factor for Cholangiocarcinoma

Cited by 10 publications

References 16 publications

NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications

NKG2D Natural Killer Cell Receptor—A Short Description and Potential Clinical Applications

Aging and biliary tract cancers: Epidemiology, molecular biology, and clinical practice

Targeting the tumor microenvironment in cholangiocarcinoma: implications for therapy

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