Induction of MHC class I-related chain B (MICB) by 5-aza-2′-deoxycytidine

Tang, Kai-Fu; He, Cai‐Xia; Zeng, Gui-Li; Wu, Jinfeng; Song, Guanbin; Shi, Yisong; Zhang, Weiguang; Huang, Ailong; Steinle, Alexander; Ren, Hong

doi:10.1016/j.bbrc.2008.03.131

Cited by 54 publications

(42 citation statements)

References 19 publications

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“…MICB expression was induced following doxorubicin treatment ( Supplementary Fig. 7) confirming previous findings 41 . Next, we transduced HFF cells with the various RBP-shRNAs and treated the cells with doxorubicin.…”

Section: Rbp-mediated Regulation Of Micb Affects Nk-mediated Killingsupporting

confidence: 90%

“…Finally, we wanted to investigate whether the RBP control of MICB expression also functions during cellular stress. We focused on the DNA-damage response as DNA damage is caused as a result of many insults (for example, exposure to ultraviolet light, viral infection and so on) and it was shown that MICB expression is induced during genotoxic stress 41 . We used the anthracycline drug Doxorubicin, which causes double-strand breaks and leads to the activation of the DNA-damage response.…”

Section: Rbp-mediated Regulation Of Micb Affects Nk-mediated Killingmentioning

confidence: 99%

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RNA-binding proteins regulate the expression of the immune activating ligand MICB

et al. 2014

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The recognition of stress-induced ligands by the activating receptor NKG2D expressed on cytotoxic lymphocytes is crucial for the prevention and containment of various diseases and is also one of the best-studied examples of how danger is sensed by the immune system. Still, however, the mechanisms leading to the expression of the NKG2D ligands are far from being completely understood. Here, we use an unbiased and systematic RNA pull-down approach combined with mass spectrometry to identify six RNA-binding proteins (RBPs) that bind and regulate the expression of MICB, one of the major stress-induced ligands of NKG2D. We further demonstrate that at least two of the identified RBPs function during genotoxic stress. Our data provide insights into stress recognition and hopefully open new therapeutic venues.

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Section: Rbp-mediated Regulation Of Micb Affects Nk-mediated Killingsupporting

confidence: 90%

Section: Rbp-mediated Regulation Of Micb Affects Nk-mediated Killingmentioning

confidence: 99%

RNA-binding proteins regulate the expression of the immune activating ligand MICB

et al. 2014

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“…15 In the setting of hypomethylating agents, upregulation of NKG2DL was attributed to promoter DNA demethylation and DNA damage and correlates with improved NK cytotoxicity. 17,18 Whether agents that upregulate NKG2DL on AML blasts could also enhance the efficacy of Fc-engineered antibodies is unknown. Here, we sought to evaluate whether hypomethylating agents such as decitabine (DAC) or azacytidine modulate susceptibility of AML blasts to Fc-engineered mAb directed against CD33.…”

Section: Introductionmentioning

confidence: 99%

Decitabine enhances anti-CD33 monoclonal antibody BI 836858–mediated natural killer ADCC against AML blasts

Vasu

Cheney

et al. 2016

Blood

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Key Points• BI 836858, an Fc-engineered anti-CD33 antibody, mediates autologous and allogeneic NK cell-mediated ADCC.• Decitabine increases ligands for activating NK receptors potentiating BI 836858 activity, providing a rationale for combination therapy.Acute myeloid leukemia (AML) is the most common type of acute leukemia, affecting older individuals at a median age of 67 years. Resistance to intensive induction chemotherapy is the major cause of death in elderly AML; hence, novel treatment strategies are warranted. CD33-directed antibody-drug conjugates (gemtuzumab ozogamicin) have been shown to improve overall survival, validating CD33 as a target for antibody-based therapy of AML.Here, we report the in vitro efficacy of BI 836858, a fully human, Fc-engineered, anti-CD33 antibody using AML cell lines and primary AML blasts as targets. BI 836858-opsonized AML cells significantly induced both autologous and allogeneic natural killer (NK)-cell degranulation and NK-cell-mediated antibody-dependent cellular cytotoxicity (ADCC). In vitro treatment of AML blasts with decitabine (DAC) or 5-azacytidine, 2 hypomethylating agents that show efficacy in older patients, did not compromise BI 836858-induced NK-cellmediated ADCC. Evaluation of BI 836858-mediated ADCC in serial marrow AML aspirates in patients who received a 10-day course of DAC (pre-DAC, days 4, 11, and 28 post-DAC) revealed significantly higher ADCC in samples at day 28 post-DAC when compared with pre-DAC treatment. Analysis of ligands to activating receptors (NKG2D) showed significantly increased NKG2D ligand [NKG2DL] expression in day 28 post-DAC samples compared with pre-DAC samples; when NKG2DL receptor was blocked using antibodies, BI 836858-mediated ADCC was significantly decreased, suggesting that DAC enhances AML blast susceptibility to BI 836858 by upregulating NKG2DL. These data provide a rationale for combination therapy of Fc-engineered antibodies such as BI 836858 with azanucleosides in elderly patients with AML.

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“…Therefore, the effect of hydralazine on the expression of Fas seems to be due to its action as a DNA methylation inhibitor. Furthermore, Tang et al (29) have shown that deoxyazocytidine induced demethylation at the MICB promoter region of HEK293T and HepG2 cells, up-regulated MICB on their cell-surface, and sensitized the cells to NK-cell-mediated cell death. In the present study, hydralazine showed the same effects as deoxyazocytidine with regard to the expression of MICA and B and the sensitization to NK cells.…”

Section: Discussionmentioning

confidence: 99%

“…Deoxyazocytidine, a DNA methylation inhibitor, also has been reported to up-regulate the expression of Fas on colon and prostatic cancer cells, and to sensitize colon cancer cells to Fas-mediated cell death (28). Furthermore, Tang et al (29) have shown that deoxycytidine increased the cell-surface MICB expression on HEK293T and HepG2 cells and sensitized them to NK cell-mediated cytotoxicity. Thus, the use of an HDAC inhibitor alone or DNA methylation inhibitor alone has been shown to enhance the susceptibility of tumor cells to cytotoxic immune cells.…”

Section: Introductionmentioning

confidence: 99%

Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death

et al. 2012

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Abstract.We investigated the effects of valproic acid (VPA), a histone deacetylase inhibitor, in combination with hydralazine, a DNA methylation inhibitor, on the expression of cell-surface Fas and MHC-class I-related chain molecules A and B (MICA and B), the ligands of NKG2D which is an activating receptor of NK cells, and on production of their soluble forms in HOS, U-2 OS and SaOS-2 human osteosarcoma cell lines. We also examined the susceptibility of these cells to Fas-and NK cellmediated cell death. VPA did not increase the expression of Fas on the surface of osteosarcoma cells, while hydralazine did, and the combination of VPA with hydralazine increased the expression of cell-surface Fas. In contrast, the combination of VPA with hydralazine did not increase the production of soluble Fas by osteosarcoma cells. Both VPA and hydralazine increased the expression of cell-surface MICA and B in osteosarcoma cells, and their combination induced a greater increase in their expression. VPA inhibited the production of both soluble MICA and MICB by osteosarcoma cells while hydralazine produced no effect. Both VPA and hydralazine enhanced the susceptibility of osteosarcoma cells to Fas-and NK cell-mediated cell death and the combination of VPA with hydralazine further enhanced the effects. The present results suggest that combined administration of VPA and hydrazine is valuable for enhancing the therapeutic effects of immunotherapy for osteosarcomas.

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Induction of MHC class I-related chain B (MICB) by 5-aza-2′-deoxycytidine

Cited by 54 publications

References 19 publications

RNA-binding proteins regulate the expression of the immune activating ligand MICB

RNA-binding proteins regulate the expression of the immune activating ligand MICB

Decitabine enhances anti-CD33 monoclonal antibody BI 836858–mediated natural killer ADCC against AML blasts

Valproic acid cooperates with hydralazine to augment the susceptibility of human osteosarcoma cells to Fas- and NK cell-mediated cell death

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