The Actin Cytoskeleton Controls the Efficiency of Killer Ig-Like Receptor Accumulation at Inhibitory NK Cell Immune Synapses

Standeven, Leah J.; Carlin, Leo M.; Borszcz, Peter; Davis, Daniel M.; Burshtyn, Deborah N.

doi:10.4049/jimmunol.173.9.5617

Cited by 42 publications

(45 citation statements)

References 47 publications

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“…3 and Video 3). In contrast, NK-cell KIR and classical HLA class I molecules from tumor cells accumulate at the site of contact [36]. Since the avidity of ILT2 for HLA-G1 has been reported to be 3-4-fold higher than for classical HLA class I molecules, HLA-G1 may not require clustering to induce an inhibitory signal [7].…”

Section: Discussionmentioning

confidence: 99%

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Baudhuin¹,

Lesport²,

Sousa³

et al. 2012

Eur J Immunol

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HLA-G is a non-classical HLA class I molecule with tolerogenic properties and restricted tissue distribution. The expression of HLA-G can be induced by tumors thus providing an efficient way to escape the anti-tumoral immune response. Although lipid rafts regulate diverse immunological mechanisms their relationship with HLA-G remains controversial. Our results show that HLA-G-mediated inhibition of both the interaction between NK and tumor cells, and of intracellular calcium flux in NK cells conjugated to their target cells were independent of lipid raft integrity. In addition, cytotoxicity assays indicated that HLA-G continued to efficiently inhibit NK-cell cytolytic function in several different tumor cells independently of lipid raft integrity. Confocal microscopy with 3D reconstruction combined with biochemical analysis showed that HLA-G was mainly localized outside the lipid rafts of tumor cells after cross-linking with specific antibody and remained excluded from lipid rafts during interaction with the ILT2 inhibitory receptor of NK cells. This study indicates that the inhibitory function of HLA-G is uncoupled from lipid raft organization, further distinguishing HLA-G from classical HLA molecules and providing novel information in the understanding of tumor immune escape mechanism mediated through HLA-G.

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Section: Discussionmentioning

confidence: 99%

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Baudhuin¹,

Lesport²,

Sousa³

et al. 2012

Eur J Immunol

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“…The molecular mechanism by which MHC class I expression can lower the susceptibility to NK cell killing has now been elucidated (11,23,24). NK cells specialize in killing non-self cells, an activity controlled by various cytokines, including IL-2 and IL-12 (12,25).…”

Section: Discussionmentioning

confidence: 99%

Immature NK Cells Suppress Dendritic Cell Functions during the Development of Leukemia in a Mouse Model

Ebata¹,

Shimizu²,

Nakayama³

et al. 2006

The Journal of Immunology

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To analyze the mechanisms by which cancer cells escape from hosts’ immune surveillance, we investigated the changes in immune status during the progression of leukemia induced by injecting mice with WEHI-3B cells. In the bone marrow (BM) of leukemic mice, only DX5+CD3− cells were continuously increased, despite the progression of leukemia. In addition, DX5+CD3− cells were rapidly increased in peripheral blood (PB) 20 days after inoculation. We also found that myeloid dendritic cells (DCs) expressing low levels of I-Ad and having low allo-T cell stimulatory activity were markedly increased in PB and spleen. The increase in DX5+ cells in BM was thought to be induced by soluble factors from leukemic cells. DX5+ cells from leukemic mice were CD3−, B220−, Gr-1−, CD14−, CD94−, Ly-49C/F−, asialo GM1+, CD25+, CD122+, Thy-1bright, and c-kitdim and showed low killing activity against YAC-1 cells, suggesting that those DX5+ cells were immature NK cells. NK cells from leukemic PB down-regulated the expression of I-Ad on DCs, an effect mediated by TGF-β. Moreover, these NK cells significantly suppressed the allo-T cell stimulatory activity of DCs, an effect requiring cell-to-cell contact between NK cells and DCs and thought to involve CD25. Importantly, NK cells from leukemic PB inhibited generation of autotumor-specific CTL induced by DCs in primary MLR or by DC immunization. In conclusion, we identified circulating immature NK cells with immunosuppressive activities. These cells may be important for understanding the involvement of the host immune system during the development of leukemia.

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“…Cell Lines and Culture Conditions Cytotoxic NK tumor cell lines Nishi (27), NKL (28), NK92 (29), and KHYG-1 (30) were cultured in IMDM supplemented with different concentrations of IL-2 (Nishi and NK92, 100 units/mL; NKL, 200 units/mL; KHYG-1, 450 units/mL). K562 cell line was used as target in the in vitro killing assay.…”

Section: Isolationand Culturingof Human Polyclonal Peripheral Blood Nmentioning

confidence: 99%

Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells

Márkász

Stuber

Vanherberghen

et al. 2007

Molecular Cancer Therapeutics

101

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Tumors are considered to be possible targets of immunotherapy using stimulated and expanded autologous or allogeneic natural killer (NK) cells mismatched for MHC class I molecules and inhibitory NK receptors. NK cellbased immunoadjuvant therapies are carried out in combination with standard chemotherapeutic protocols. In the presented study, we characterized the effect of 28 frequently used chemotherapeutic agents on the capacity of NK cells to kill target cells. We found that treatment of NK cells with the drugs vinblastine, paclitaxel, docetaxel, cladribine, chlorambucil, bortezomib, and MG-132 effectively inhibited NK cell -mediated killing without affecting the viability of NK cells. On the other hand, the following drugs permitted efficient NK cell -mediated killing even at concentrations comparable with or higher than the maximally achieved therapeutic concentration in vivo in humans: asparaginase, bevacizumab, bleomycin, doxorubicin, epirubicin, etoposide, 5-fluorouracil, hydroxyurea, streptozocin, and 6-mercaptopurine. [Mol Cancer Ther 2007;6(2):644 -54]

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The Actin Cytoskeleton Controls the Efficiency of Killer Ig-Like Receptor Accumulation at Inhibitory NK Cell Immune Synapses

Cited by 42 publications

References 47 publications

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Immature NK Cells Suppress Dendritic Cell Functions during the Development of Leukemia in a Mouse Model

Effect of frequently used chemotherapeutic drugs on the cytotoxic activity of human natural killer cells

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