Primary Human Tumor Cells Expressing CD155 Impair Tumor Targeting by Down-Regulating DNAM-1 on NK Cells

Carlsten, Mattias; Norell, Håkan; Bryceson, Yenan T.; Poschke, Isabel; Schedvins, Kjell; Ljunggren, Hans‐Gustaf; Kiessling, Rolf; Malmberg, Karl‐Johan

doi:10.4049/jimmunol.0901226

Cited by 230 publications

(240 citation statements)

References 60 publications

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“…25 We recently reported that NK cells loose the expression of DNAM-1 after physical interactions with target cells expressing the DNAM-1 ligand, CD155. 24 Similar mechanisms could be operating in MDS, as we here show that the reduction of DNAM-1 expression was more pronounced in the bone marrow of patients with high counts of CD34 þ blasts that all express CD155. In contrast, we believe that it is unlikely that such receptor-ligand interactions mediate the downregulation of NKG2D as the CD34 þ blasts rarely express NKG2D ligands.…”

Section: Discussionsupporting

confidence: 70%

“…All cells were frozen following collection and thawed before usage, as previously described. 24 The human erythroleukemia cell line K562 and the mouse mastocytoma cell line P815 (American Type Culture Collection (ATCC), Manassas, VA, USA) were maintained in complete medium (RPMI 1640 containing 100 mg/ml L-glutamine, 10% heat-inactivated fetal bovine serum, 100 U/ml penicillin G and 100 mg/ml streptomycin).…”

Section: Patients and Cellsmentioning

confidence: 99%

“…In addition, reduced surface expression of DNAM-1 and NKG2D has recently been observed and associated with impaired NK-cell cytotoxicity in patients with advanced cancer. [22][23][24][25][26] Previous studies have shown reduced peripheral blood NK-cell function in MDS patients. 25,[27][28][29] In one such study, reduced NK-cell function was described in patients with all subtypes of MDS, despite intact expression of activating NK-cell receptors.…”

Section: Introductionmentioning

confidence: 99%

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Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome

Carlsten

Simonsson

et al. 2010

Leukemia

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Myelodysplastic syndromes (MDS) comprise a heterogeneous group of clonal stem-cell disorders characterized by ineffective hematopoiesis and risk of progression to acute myeloid leukemia. Increased apoptosis and suppressed functions of peripheral blood natural killer (NK) cells have been described in MDS patients, but only limited information is available on the phenotypic and functional integrity of NK cells in the bone marrow. In a cohort of 41 patients with distinct clinical subtypes of MDS, we here show that NK cells in the bone marrow show decreased surface expression of the activating receptors DNAM-1 and NKG2D. Notably, decreased receptor expression correlated with elevated bone marrow blast counts and was associated with impaired NK-cell responsiveness to stimulation with the K562 cell line, or co-activation by NKG2D or DNAM-1 in combination with the 2B4 receptor. Furthermore, antibodymasking experiments revealed a central role for DNAM-1 in NK cell-mediated killing of freshly isolated MDS blasts. Thus, given the emerging evidence for NK cell-mediated immune surveillance of neoplastic cells, we speculate that reduced expression of DNAM-1 on bone marrow NK cells may facilitate disease progression in patients with MDS.

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Section: Discussionsupporting

confidence: 70%

Section: Patients and Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome

Carlsten

Simonsson

et al. 2010

Leukemia

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“…In an autologous setting, normal cells are spared from NK-mediated killing because of the expression of high (protective) amounts of self-HLA class I molecules and of the lack of (or low) expression of ligands for activating NK receptors. However, tumors become susceptible to killing mediated by autologous NK cells because of a defective (nonprotective) expression of HLA class I molecules and de novo expression or up-regulation of ligands for activating NK receptors (6,7,9,11,12).…”

mentioning

confidence: 99%

The interaction of human natural killer cells with either unpolarized or polarized macrophages results in different functional outcomes

Bellora

Castriconi

Dondero

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

204

220

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The cross-talk among cells of the innate immunity can greatly affect both innate and adaptive responses. Here we analyzed the molecular interactions between human natural killer (NK) cells and autologous macrophages. Activated NK cells killed M0 and M2, whereas M1 macrophages were more resistant to lysis because of their higher expression of HLA class I molecules. Following exposure to LPS or bacillus Calmette-Guérin, M0 and M2, but not polarized (endotoxin tolerant) M1 macrophages, induced strong activation of resting NK cells. The expression of CD69 and CD25 activation markers and the acquisition of cytotoxicity against tumor cells and immature dendritic cells required soluble factors being mostly contact independent. On the contrary, IFN-γ production was contact dependent and required the interaction of DNAM-1 and 2B4 (on NK) with their ligands on macrophages as well as IL-18. IL-18 was involved also in the acquisition of CCR7 by NK cells. Interestingly, M0 and M2 cells expressed a membrane-bound form of IL-18, which was released in small amounts after LPS treatment. Our data indicate that, upon interaction with M0 macrophages exposed to microbial products, NK cells may amplify classical type 1 immune responses. In addition, M1-polarizing stimuli can rescue M2 macrophages from their immunomodulatory state and shape their functional behavior toward NK stimulatory capability.cytolityc activity | proinflammatory cytokines | lypopolissacaride | molecular interactions | nectins' family

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“…Indeed, fibroblasts derived from melanoma lesions were found to inhibit, by mean of cell-to-cell contact and PGE 2 release, the IL-2-driven up-regulation of NKp44, DNAM-1 and NKp30 on NK cells Chiesa et al, 2006). In addition, tumor cells can also induce down-regulation of NKG2D or DNAM-1 on NK cells by the release of soluble NKG2D-Ligands (Doubrovina et al, 2003) or by the prolonged engagement of DNAM-1 in cell-to-cell contact (Carlsten et al, 2009) …”

Section: Role Of Nk Cells In the Control Of Tumorsmentioning

confidence: 99%

Physiological and Pathological Aspects of Human NK Cells

Vitale¹,

Zambello²,

Balsamo³

et al. 2012

Hematology - Science and Practice

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Primary Human Tumor Cells Expressing CD155 Impair Tumor Targeting by Down-Regulating DNAM-1 on NK Cells

Abstract: Material

Cited by 230 publications

References 60 publications

Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome

Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34+ blasts in myelodysplastic syndrome

The interaction of human natural killer cells with either unpolarized or polarized macrophages results in different functional outcomes

Physiological and Pathological Aspects of Human NK Cells

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