原创力文档histone deacetylase inhibitors enhance expression of nkg2d ligands in ewing sarcoma and sensitize for natural killer cell-mediated cytolysis组蛋白脱乙酰酶抑制剂增强表达nkg2d配基在尤因肉瘤和自然杀伤细胞介导细胞溶解进行宣传.pdfVIP
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histone deacetylase inhibitors enhance expression of nkg2d ligands in ewing sarcoma and sensitize for natural killer cell-mediated cytolysis组蛋白脱乙酰酶抑制剂增强表达nkg2d配基在尤因肉瘤和自然杀伤细胞介导细胞溶解进行宣传
Berghuis et al. Clinical Sarcoma Research 2012, 2:8
/content/2/1/8 CLINICAL SARCOMA RESEARCH
RESEARCH Open Access
Histone deacetylase inhibitors enhance
expression of NKG2D ligands in Ewing sarcoma
and sensitize for natural killer cell-mediated
cytolysis
1,2 2 2 2 3 2
Dagmar Berghuis , Marco W Schilham , Hanneke I Vos , Susy J Santos , Stephan Kloess , Emilie P Buddingh’ ,
R Maarten Egeler2, Pancras CW Hogendoorn1 and Arjan C Lankester2*
Abstract
Background: Ewing sarcoma patients have a poor prognosis despite multimodal therapy. Integration of
combination immunotherapeutic strategies into first-/second-line regimens represents promising treatment options,
particularly for patients with intrinsic or acquired resistance to conventional therapies. We evaluated the
susceptibility of Ewing sarcoma to natural killer cell-based combination immunotherapy, by assessing the capacity
of histone deacetylase inhibitors to improve immune recognition and sensitize for natural killer cell cytotoxicity.
Methods: Using flow cytometry, ELISA and immunohistochemistry, expression of natural killer cell receptor ligands
was assessed in chemotherapy-sensitive/-resistant Ewing sarcoma cell lines, plasma and tumours. Natural killer cell
cytotoxicity was evaluated in Chromium release assays. Using ATM/ATR inhibitor caffeine, the contribution of the
DNA damage response pathway to histone deacetylase inhibitor-induced ligand expression was assessed.
Results: Despite comparable expression of natural killer cell receptor ligands, chemotherapy-resistant Ewing
sarcoma exhibited reduced susceptibility to resting natural killer cells. Interleukin-15-activation of natural kil
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