Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation

Groh, Veronika; Wu, Jennifer D.; Yee, Cassian; Spies, Thomas A.

doi:10.1038/nature01112

Cited by 1,393 publications

(1,349 citation statements)

References 18 publications

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“…Our results suggest that the escape mechanism is more complex due to the concomitant NK-cell activation, the ensuing NKG2D modulation and the poorly understood reciprocity of NKG2D down-regulation and NKG2D-L loss. Shedding of soluble NKG2D-L can lead to down-regulation of NKG2D and protection from NK-cell attack in cancer patients [39]. Although we cannot rule out the presence of soluble NKG2D-L in sera of tumor mice, direct cell contacts are most likely to account for NKG2D modulation (Fig.…”

Section: Discussionmentioning

confidence: 95%

Requirements for control of B‐cell lymphoma by NK cells

et al. 2010

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The role of NK cells in the control of endogenously arising tumors is still unclear. We monitored activation and effector functions of NK cells in a c‐myc‐transgenic mouse model of spontaneously arising lymphoma. At early stages, tumors demonstrated reduced MHC class I expression and increased expression of natural killer group 2D ligands (NKG2D‐L). NK cells in these tumors showed an activated phenotype that correlated with the loss of tumor MHC class I. With increasing tumor load however, NK‐cell effector functions became progressively paralyzed or exhausted. In later stages of disease, tumors re‐expressed MHC class I and lost NKG2D‐L, suggesting a role of these two signals for NK cell‐mediated tumor control. Testing a panel of lymphoma cell lines expressing various MHC class I and NKG2D‐L levels suggested that NK cell‐dependent tumor control required a priming and a triggering signal that were provided by MHC class I down‐regulation and by NKG2D‐L, respectively. Deleting either of the “two signals” resulted in tumor escape. At early disease stages, immune stimulation through TLR‐ligands in vivo efficiently delayed lymphoma growth in a strictly NK cell‐dependent manner. Thus, NK‐receptor coengagement is crucial for NK‐cell functions in vivo and especially for NK cell‐mediated tumor surveillance.

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Section: Discussionmentioning

confidence: 95%

Requirements for control of B‐cell lymphoma by NK cells

et al. 2010

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“…This might be another way for tumor cells to avoid eradication by NK and  T cells. NKG2D has also been shown to act as a co-receptor allowing the destruction of tumor cells by cytotoxic T cells (CTL) [47]. The present study did not investigate the ability of PGE 2 to inhibit NKG2D co-activation of CTL.…”

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confidence: 86%

PGE2 inhibits natural killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling

Martinet¹,

Jean²,

Dietrich³

et al. 2010

Biochemical Pharmacology

108

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inhibits Natural Killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMPmediated PKA type I-dependent signaling. Biochemical Pharmacology, Elsevier, 2010, 80 (6) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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“…37-40 In this context, soluble ligands, endowed with suppressive capability, have been described for NKG2D and DNAM-1 activating receptors (sMICA, sULBPs, and sPVR) and for NKp30 (sB7H6 and sBAT3/BAG6). 32,33,35,41-50 On the other hand, extracellular ligands for NKp46 and NKp44 have been recently identified and demonstrated to have a positive effect on the NK cell function. NKp46 has been shown to bind an extracellular molecule: the Complement Factor P (CFP or properdin).…”

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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Tumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation

Cited by 1,393 publications

References 18 publications

Requirements for control of B‐cell lymphoma by NK cells

Requirements for control of B‐cell lymphoma by NK cells

PGE2 inhibits natural killer and γδ T cell cytotoxicity triggered by NKR and TCR through a cAMP-mediated PKA type I-dependent signaling

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

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