Human Leukocyte Antigen-B-Associated Transcript 3 Is Released from Tumor Cells and Engages the NKp30 Receptor on Natural Killer Cells

Strandmann, Elke Pogge von; Simhadri, Venkateswara R.; Tresckow, Bastian von; Sasse, Stephanie; Reiners, Katrin S.; Hansen, Hinrich P.; Rothe, Achim; Böll, Boris; Simhadri, Vijaya L.; Borchmann, Peter; McKinnon, Peter J.; Hallek, Michael; Engert, Andreas

doi:10.1016/j.immuni.2007.10.010

Cited by 292 publications

(266 citation statements)

References 43 publications

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“…29,30 NKp30 triggers cytotoxicity and cytokine release upon binding B7H6 or BAT3 at the cell surface. 24,25,31 Besides NCRs, other activating receptors, including NKG2D and DNAM-1, contribute to trigger the NK cell-mediated cytotoxicity. 32-34 Ligands specific for these receptors have been extensively characterized: MICA/B and ULBPs molecules are recognized by NKG2D, while PVR and Nectin-2 (belonging to the Nectin family), are ligands for DNAM-1.…”

Section: Introductionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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The release of soluble ligands of activating Natural Killer (NK) cell receptors may represent a regulatory mechanism of NK cell function both in physiologic and in pathologic conditions. Here, we identified the extracellular matrix protein Nidogen-1 (NID1) as a ligand of NKp44, an important activating receptor expressed by activated NK cells. When released as soluble molecule, NID1 regulates NK cell function by modulating NKp44-induced IFN-γ production or cytotoxicity. In particular, it also modulates IFN-γ production induced by Platelet-Derived Growth Factor (PDGF)-DD following NKp44 engagement. We also show that NID1 may be present at the cell surface. In this form or when bound to a solid support (bNID1), NID1 fails to induce NK cell cytotoxicity or cytokine release. However, analysis by mass spectrometry revealed that exposure to bNID1 can induce in human NK cells relevant changes in the proteomic profiles suggesting an effect on different biological processes.

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Section: Introductionmentioning

confidence: 99%

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

et al. 2018

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“…8) are activating receptors (collectively named 'natural cytotoxicity receptors' (NCRs)) that play a major role in tumour cell recognition and killing by NK cells 9 . Although NCRs were found to bind some viral glycoproteins, their ligands on tumour cells have only partially been defined 10,11 . B7-H6 and, very recently, a novel isoform of the mixed-lineage leukemia (MLL5) protein have been shown to be expressed on a large panel of tumour cells 12,13 and are recognized by NKp30 and NKp44 receptors, respectively.…”

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confidence: 99%

NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures

et al. 2015

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Tertiary lymphoid structures (TLSs) are a common finding in non-small cell lung cancer (NSCLC) and are predictors of favourable clinical outcome. Here we show that NCR þ innate lymphoid cell (ILC)-3 are present in the lymphoid infiltrate of human NSCLC and are mainly localized at the edge of tumour-associated TLSs. This intra-tumoral lymphocyte subset is endowed with lymphoid tissue-inducing properties and, on activation, produces IL-22, TNF-a, IL-8 and IL-2, and activates endothelial cells. Tumour NCR þ ILC3 may interact with both lung tumour cells and tumour-associated fibroblasts, resulting in the release of cytokines primarily on engagement of the NKp44-activating receptor. In patients, NCR þ ILC3 are present in significantly higher amounts in stage I/II NSCLC than in more advanced tumour stages and their presence correlate with the density of intratumoral TLSs. Our results indicate that NCR þ ILC3 accumulate in human NSCLC tissue and might contribute to the formation of protective tumour-associated TLSs.

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“…NKp30-specific ligands are expressed on different types of tumors that have been demonstrated to be lysed by NK cells in an NKp30-dependent manner (8,(12)(13)(14)(15). Ligation of NKp30, moreover, has been shown to trigger the release of immunostimulatory cytokines such as TNF-a and IFN-g (16,17).…”

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confidence: 99%

Mimicking an Induced Self Phenotype by Coating Lymphomas with the NKp30 Ligand B7-H6 Promotes NK Cell Cytotoxicity

Kellner

Maurer

Hallack

et al. 2012

The Journal of Immunology

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Induced self expression of the NKp30 ligand B7-H6 facilitates NK cell-mediated elimination of stressed cells. A fusion protein consisting of the ectodomain of B7-H6 and the CD20 single-chain fragment variable 7D8 was generated to mimic an induced self phenotype required for NK cell-mediated target cell elimination. B7-H6:7D8 had bifunctional properties as reflected by its ability to simultaneously bind to the CD20 Ag and to the NKp30 receptor. B7-H6:7D8 bound by CD20+ lymphoma cells activated human NK cells and triggered degranulation. Consequently, the immunoligand B7-H6:7D8 induced killing of lymphoma-derived cell lines as well as fresh tumor cells from chronic lymphocytic leukemia or lymphoma patients. B7-H6:7D8 was active at nanomolar concentrations in a strictly Ag-specific manner and required interaction with both CD20 and NKp30. Remarkably, NK cell cytotoxicity was further augmented by concomitant activation of Fcγ receptor IIIa or NK group 2 member D. Thus, B7-H6:7D8 acted synergistically with the CD20 Ab rituximab and the immunoligand ULBP2:7D8, which was similarly designed as B7-H6:7D8 but engaging the NK group 2 member D receptor. In conclusion, to our knowledge, B7-H6:7D8 represents the first Ab-based molecule stimulating NKp30-mediated NK cell cytotoxicity for therapeutic purposes and provides proof of concept that Ag-specific NKp30 engagement may represent an innovative strategy to enhance antitumoral NK cell cytotoxicity.

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Human Leukocyte Antigen-B-Associated Transcript 3 Is Released from Tumor Cells and Engages the NKp30 Receptor on Natural Killer Cells

Cited by 292 publications

References 43 publications

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

Nidogen-1 is a novel extracellular ligand for the NKp44 activating receptor

NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures

Mimicking an Induced Self Phenotype by Coating Lymphomas with the NKp30 Ligand B7-H6 Promotes NK Cell Cytotoxicity

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