NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution

Messaoudene, Meriem; Fregni, Giulia; Enot, David; Jacquelot, Nicolas; Neves, E.; Germaud, Nathalie; Garchon, Henri Jean; Boukouaci, Wahid; Tamouza, Ryad; Chanal, J.; Avril, Marie-Françoise; Toubert, Antoine; Zitvogel, Laurence; Rusakiewicz, Sylvie; Caignard, Anne

doi:10.1080/2162402x.2016.1154251

Cited by 20 publications

(27 citation statements)

References 28 publications

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“…The potential prognostic value of NKp30 isoforms was also recently investigated in melanoma patients (100). The overall mRNA expression levels of each of the NKp30 isoforms were found to be reduced compared to expression in healthy donors, but expression ratios between the isoforms did not differ.…”

Section: Splice Variants Of Ncrs Resulting In Distinct Receptor Isoformsmentioning

confidence: 99%

“…In accordance with this finding, the long-term survivors were more likely to have SNPs associated with reduced expression of suppressive NKp30c and increased expression of NKp30a. Furthermore, NK cells from long-term surviving patients exhibited increased degranulation potential in response to NKp30 stimulation (100). Therefore, higher expression of NKp30a in melanoma patients appears to be beneficial.…”

Section: Splice Variants Of Ncrs Resulting In Distinct Receptor Isoformsmentioning

confidence: 99%

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Regulation of the Functions of Natural Cytotoxicity Receptors by Interactions with Diverse Ligands and Alterations in Splice Variant Expression

et al. 2017

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The natural cytotoxicity receptor (NCR) family is constituted by NKp46, NKp44, and NKp30 in humans, which are expressed mainly on natural killer (NK) cells and are encoded by the ncr1, ncr2, and ncr3 genes, respectively. NCRs have classically been defined as activating receptors that trigger cytotoxicity and cytokine responses by NK cells upon engaging with ligands on tumor cells. Several new findings, however, have challenged this model and identified alternative mechanisms regulating the function of NCRs. Recent reports indicate that ligand matters, since the interaction of NKp44 with distinct ligands on target cells can either activate or inhibit NK cells. Also, the NCRs have been found to interact with distinct specificities to various heparan sulfate glycosaminoglycans, which are complex polysaccharides found in extracellular matrix or on cell surface heparan sulfate proteoglycans (HSPGs). The NCRs can engage with HSPGs in trans as a co-ligand on the target cells or in cis on the NK cell surface to regulate receptor–ligand interactions and NK cell activation. A number of splice variants of ncr2 and ncr3 have also been identified, and a predominant expression of certain variants results in inhibitory signaling through NKp44 and NKp30. Several recent studies have found that the selective expression of some of these inhibitory splice variants can significantly influence outcome in the contexts of cancer, infection, and pregnancy. These findings establish that NCR functions are more diverse than originally thought, and better understanding of their splice variant expression profiles and ligand interactions are needed to establish their functional regulation in the context of human health.

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Section: Splice Variants Of Ncrs Resulting In Distinct Receptor Isoformsmentioning

confidence: 99%

Section: Splice Variants Of Ncrs Resulting In Distinct Receptor Isoformsmentioning

confidence: 99%

Regulation of the Functions of Natural Cytotoxicity Receptors by Interactions with Diverse Ligands and Alterations in Splice Variant Expression

et al. 2017

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“…Functional NK cell deficiency might also be associated with an increased regulatory T‐cell frequency, an altered dendritic cell function, and an increased proportion of myeloid‐derived suppressor cells . Apart from those mechanisms, alternative splicing of the NCR3 gene has been shown to profoundly influence NKp30‐dependent function and has been correlated with the prognosis and evolution in gastrointestinal stromal tumor patients as well as other cancers, viral infections, and miscarriage . However, no information is currently available on NCR3 splice variant profile and function in liver cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The NKp30a and NKp30b isoforms are considered to be immunostimulatory, as they induce cytotoxicity and Th1 cytokine secretion, respectively, whereas the NKp30c isoform shows an immunosuppressive activity triggering interleukin (IL)‐10 release. Furthermore, the relative abundance of the mRNA encoding the NKp30c isoform compared with isoform a or b can negatively affect the prognosis and evolution of different malignancies and might be associated with advanced liver disease in hepatitis C virus (HCV)‐infected patients . Moreover, the expression of different NCR3 splice variants by NK cells delineates functionally distinct subsets and is governed by the cytokine‐defined microenvironment .…”

mentioning

confidence: 99%

“…Furthermore, the relative abundance of the mRNA encoding the NKp30c isoform compared with isoform a or b can negatively affect the prognosis and evolution of different malignancies and might be associated with advanced liver disease in hepatitis C virus (HCV)-infected patients. (5)(6)(7)(8) Moreover, the expression of different NCR3 splice variants by NK cells delineates functionally distinct subsets and is governed by the cytokine-defined microenvironment. (9,10) The NKp30 receptor recognizes the human leukocyte antigen-B-associated transcript 3, the human cytomegalovirus pp65 tegument protein, and the cell surface protein B7 homolog 6 (B7-H6), a member of the B7 family of receptors.…”

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confidence: 99%

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Deficient Natural Killer Cell NKp30‐Mediated Function and Altered NCR3 Splice Variants in Hepatocellular Carcinoma

et al. 2019

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Splice variants of human natural cytotoxicity receptors: novel innate immune checkpoints

Shemesh

Brusilovsky

Kundu

et al. 2017

Cancer Immunol Immunother

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The natural cytotoxicity receptors (NCRs; NKp30, NKp44, and NKp46) were first defined as activating receptors on human NK cells that are important in recognition of and response to tumors. A flurry of recent research, however, has revealed that differential splicing can occur during transcription of each of the NCR genes, resulting in some transcripts that encode receptor isoforms with inhibitory functions. These alternative transcripts can arise in certain tissue microenvironments and appear to be induced by cytokines. Evidence indicates that some of the inhibitory NCRs are triggered by specific ligands, such as the interaction of the inhibitory isoform of NKp44 with PCNA on the surface of tumor cells. Here, we review the different NCR splice variants, cytokines that modulate their expression, their functional impacts on innate immune cells, and their differential expression in the contexts of cancer, pregnancy, and infections. The recent discovery of these inhibitory NCR isoforms has revealed novel innate immune checkpoints, many of which still lack defined ligands and clear mechanisms driving their expression. These NCR checkpoint pathways offer exciting potential therapeutic targets to manipulate innate immune functions under defined pathological conditions, such as cancer, pregnancy disorders, and pathogen exposure.

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NKp30 isoforms and NKp46 transcripts in metastatic melanoma patients: Unique NKp30 pattern in rare melanoma patients with favorable evolution

Cited by 20 publications

References 28 publications

Regulation of the Functions of Natural Cytotoxicity Receptors by Interactions with Diverse Ligands and Alterations in Splice Variant Expression

Regulation of the Functions of Natural Cytotoxicity Receptors by Interactions with Diverse Ligands and Alterations in Splice Variant Expression

Deficient Natural Killer Cell NKp30‐Mediated Function and Altered NCR3 Splice Variants in Hepatocellular Carcinoma

Splice variants of human natural cytotoxicity receptors: novel innate immune checkpoints

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