Soluble MICA as an independent prognostic factor for the overall survival and progression-free survival of multiple myeloma patients

Rebmann, Vera; Schütt, Philipp; Brandhorst, Dieter; Opalka, Bertram; Möritz, Thomas; Nowrousian, Mohammad Reza; Grosse‐Wilde, H.

doi:10.1016/j.clim.2006.11.007

Cited by 85 publications

(92 citation statements)

References 26 publications

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“…However, we did find a negative correlation of sMICA and sULBP2 with the relative number of peripheral blood NK cells in CLL patients as already described for MM. 29 The low number of NK cells in CLL patients is in agreement with a recent study suggesting NK and T-cell count as prognostic factors for the prediction of TFS. 43 Further studies will have to validate whether other mechanisms than sMIC-induced endocytosis or degradation of NKG2D are operative as immune escape mechanisms.…”

Section: Discussionsupporting

confidence: 78%

“…22,24,29 For MM, sMICA is described as an independent prognostic marker for OS and progression-free survival. 22,24,29 This study clearly shows Soluble NKG2D ligands in chronic lymphocytic leukemia H Nückel et al that sULBP2 rather than sMICA or sMICB is of prognostic relevance for disease progression and OS of CLL patient. Moreover, we were able to identify sULBP2 but not sMICA or sMICB as a new independent prognostic marker for disease progression.…”

Section: Discussionmentioning

confidence: 99%

“…Elevated sMICA levels seem to be associated with an enhanced risk of disease progression in MM patients with disease stage I. 29 Thus, the NKG2D/NKG2DL system fulfills all criteria of an ideal prognostic parameter: (i) it is relevant in the immune biology of tumors; (ii) it represents target molecules for new therapeutic approaches; and (iii) it can be used to identify patients with high risk of early disease progression.…”

Section: Introductionmentioning

confidence: 99%

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The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia

et al. 2010

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Soluble or membrane-anchored ligands of NKG2D and their receptor have a critical role in the elimination of tumor cells and disease progression. Plasma samples of 98 patients with B-cell chronic lymphocytic leukemia (CLL) were analyzed with specific ELISA systems for soluble major histocompatibility complex class I-related chains (sMICA and sMICB) and UL-16-binding proteins (ULBP1, 2, and 3). The flow cytometric analysis of MICA on CLL cells and natural killer group 2 member D (NKG2D) receptors on NK cells was performed after thawing of frozen peripheral blood lymphocytes of CLL patients (N ¼ 51). Levels of sMICA, sMICB, and sULBP2 were significantly increased (Po0.001) compared with 48 controls, whereas sULBP1 3 were not detectable in patients and controls. Levels of sMICA4990 pg/ml (P ¼ 0.014), sMICB4200 pg/ml (P ¼ 0.0001), and sULBP24105 pg/ml (Po0.0001) were associated with poor treatment-free survival (TFS). Neither MICA nor NKG2D expression could be related to clinical parameters. In multivariate analysis Binet stage (P ¼ 0.002), sULBP2 (P ¼ 0.002) and ZAP-70 (P ¼ 0.002) were independent predictive factors for TFS. In patients with Binet stage A, sULBP2 levels4105 pg/ml were strongly associated (P ¼ 0.0025) with poor TFS. Our data show that soluble but not membrane-anchored NKG2D ligands or receptors are of prognostic significance in CLL. Moreover, sULBP2 seems to be useful to identify early-stage patients with risk of disease progression.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia

et al. 2010

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“…Indeed, soluble forms of NKG2DLs are present in the serum of cancer patients, and their levels correlate with tumor stage and metastasis (12,20,21,(38)(39)(40)(41), as well as with reduced expression of NKG2D on NK cells and other cytotoxic lymphocytes (11,21,42).…”

Section: Discussionmentioning

confidence: 99%

“…NKG2D was reported to play an important role in the NK cell-mediated killing of MM cells (17)(18)(19), and high levels of sMICA in sera of MM patients correlate with the disease stage, strongly suggesting sMICA as an independent prognostic factor in newly diagnosed MM patients (20,21).…”

mentioning

confidence: 99%

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Zingoni

Cecere

Vulpis

et al. 2015

The Journal of Immunology

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Genotoxic stress can promote antitumor NK cell responses by upregulating the surface expression of activating ligands on cancer cells. Moreover, a number of studies suggested a role for soluble NK group 2D ligands in the impairment of NK cell tumor recognition and killing. We investigated whether genotoxic stress could promote the release of NK group 2D ligands (MHC class I-related chain [MIC]A and MICB), as well as the molecular mechanisms underlying this event in human multiple myeloma (MM) cells. Our results show that genotoxic agents used in the therapy of MM (i.e., doxorubicin and melphalan) selectively affect the shedding of MIC molecules that are sensitive to proteolytic cleavage, whereas the release of the short MICA*008 allele, which is frequent in the white population, is not perturbed. In addition, we found that a disintegrin and metalloproteinase 10 expression is upregulated upon chemotherapeutic treatment both in patient-derived CD138(+)/CD38(+) plasma cells and in several MM cell lines, and we demonstrate a crucial role for this sheddase in the proteolytic cleavage of MIC by means of silencing and pharmacological inhibition. Interestingly, the drug-induced upregulation of a disintegrin and metalloproteinase 10 on MM cells is associated with a senescent phenotype and requires generation of reactive oxygen species. Moreover, the combined use of chemotherapeutic drugs and metalloproteinase inhibitors enhances NK cell-mediated recognition of MM cells, preserving MIC molecules on the cell surface and suggesting that targeting of metalloproteinases in conjunction with chemotherapy could be exploited for NK cell-based immunotherapeutic approaches, thus contributing to avoid the escape of malignant cells from stress-elicited immune responses

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Blockade of NKG2D ameliorates disease in mice with collagen‐induced arthritis: A potential pathogenic role in chronic inflammatory arthritis

Andersson¹,

Sumariwalla²,

McCann³

et al. 2011

Arthritis & Rheumatism

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Objective. To assess the role of the activating receptor NKG2D in arthritis.Methods. Levels of NKG2D and its ligands were determined by fluorescence-activated cell sorting, realtime polymerase chain reaction, and immunohistochemistry in rheumatoid arthritis (RA) synovial membrane tissue and in paw tissue from arthritic mice. Arthritis was induced in DBA/1 mice by immunization with type II collagen, and mice were treated intraperitoneally with a blocking anti-NKG2D antibody (CX5) on days 1, 5, and 8 after clinical onset and were monitored for 10 days.Results. We demonstrated expression of NKG2D Natural killer (NK) cells are lymphocytes of the innate immune system with both cytotoxic and cytokineproducing effector functions, regulated by a repertoire of cell receptors, including activating receptors NKG2D, CD16 (Fc␥ receptor III), NKp30, NKp44, and NKp46; killer cell immunoglobulin-like receptor; and the inhibitory receptors CD94/NKG2A and LY49 (mouse) (for review, see ref. 1). The role of NK cells in the defense against infections and cancer has been studied extensively (1), but their role in autoimmunity and chronic

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Soluble MICA as an independent prognostic factor for the overall survival and progression-free survival of multiple myeloma patients

Cited by 85 publications

References 26 publications

The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia

The prognostic significance of soluble NKG2D ligands in B-cell chronic lymphocytic leukemia

Genotoxic Stress Induces Senescence-Associated ADAM10-Dependent Release of NKG2D MIC Ligands in Multiple Myeloma Cells

Blockade of NKG2D ameliorates disease in mice with collagen‐induced arthritis: A potential pathogenic role in chronic inflammatory arthritis

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