2009
DOI: 10.4049/jimmunol.0901797
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Heat Shock Protein-90 Inhibitors Increase MHC Class I-Related Chain A and B Ligand Expression on Multiple Myeloma Cells and Their Ability to Trigger NK Cell Degranulation

Abstract: Modulation of the host immune system represents a promising therapeutic approach against cancer, including multiple myeloma. Recent findings indicate that the NK group 2D (NKG2D)- and DNAX accessory molecule-1 (DNAM-1)-activating receptors play a prominent role in tumor recognition and elimination by cytotoxic lymphocytes, suggesting that the levels of NKG2D and DNAM-1 ligand expression on tumor cells may be a critical factor to improve the immune response against cancer. In this study, we tested the effect of… Show more

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Cited by 78 publications
(77 citation statements)
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References 49 publications
(58 reference statements)
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“…Enhancement of NK cell-mediated recognition of MM cells was reported by us and other investigators, showing increased surface expression of NKG2DLs on tumor cells following treatment with genotoxic agents (22) or with GSK3, HSP-90, and histone deacetylase inhibitors (23)(24)(25). Importantly, drug-induced expression of these ligands on MM cells was always associated with their ability to trigger increased NK cell degranulation in an NKG2D-dependent manner.…”
supporting
confidence: 66%
“…Enhancement of NK cell-mediated recognition of MM cells was reported by us and other investigators, showing increased surface expression of NKG2DLs on tumor cells following treatment with genotoxic agents (22) or with GSK3, HSP-90, and histone deacetylase inhibitors (23)(24)(25). Importantly, drug-induced expression of these ligands on MM cells was always associated with their ability to trigger increased NK cell degranulation in an NKG2D-dependent manner.…”
supporting
confidence: 66%
“…Chromatin was prepared as previously described (21). After removing an aliquot (input), chromatin samples were incubated at 4˚C overnight with Abs against E2F1 or control IgG.…”
Section: Chromatin Immunoprecipitation Assaymentioning
confidence: 99%
“…The mechanisms that control the expression of NKG2D and DNAM-1 ligands are only partially known and are largely dependent on the cell type and stressors including heat shock, UV and oxidative and proteoxic stress, DNA damaging, and chromatin remodeling agents ( [8][9][10][11][12] ). Regulation of NKG2D and DNAM-1 ligand expression mainly occurs at transcriptional level.…”
Section: Introductionmentioning
confidence: 99%