Activation of HLA-G expression by 5-aza-2´- deoxycytidine in malignant hematopoetic cells isolated from leukemia patients

Poláková, K; Bandžuchová, E; Fa, Sabty; Mistrík, Martin; Demitrovicova, Ludmila; Russ, G

doi:10.4149/neo_2009_06_514

Cited by 16 publications

(10 citation statements)

References 30 publications

(44 reference statements)

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“…CT using platinum compounds or paclitaxel showed significant reduction of HLA-G expression in tumor cells in patients with ovarian carcinoma [93]. In contrast, 5-aza-2 -deoxycytidine enhanced HLA-G in leukemia cells [97]. HLA-G was downregulated in basal cell carcinomas of the skin after RT [98].…”

Section: The Effect Of Ct/rt On Hla Molecule Expressionmentioning

confidence: 96%

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

Rosental¹,

Appel²,

Yossef³

et al. 2012

CMC

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In recent years, the effects of cancer chemotherapy and radiotherapy (CT/RT) regimens as they apply to the immune system have been explored. NK cells represent the main cytotoxic arm of the innate immune system, and their functionality is vital to establishing an effective anti tumor immune response. This review examines current CT/RT interventions in light of their effects on NK cell functionality. The effects of CT/RT on the expression of the various ligands for activating and inhibitory NK cell receptors are discussed. Expression of ligands for the activating NKG2D receptor is enhanced by cell stress; accordingly there are numerous reports of their higher expression in cells exposed to various CT/RT agents. In contrast, some agents have been reported to cause ligand shedding, which can serve to inhibit NK cell activity. Reported effects of CT/RT on tumor expression of ligands for the activating Natural Cytotoxicity Receptors, and of HLA class I ligands for NK cell inhibitory receptors are also noted. Additionally, we describe reports concerning the direct effects of CT/RT on NK cell function. Many treatments adversely affect NK cell function directly, but observations made through in vitro systems may differ from those obtained utilizing clinical samples. The effects of CT/RT on both direct NK cell cytotoxicity and on NK cell-mediated Antibody Dependent Cellular Cytotoxicity are explored. Taken together, CT/RT affects NK cell anti-tumor immunity from multiple angles. The interplay is complex, and future work is needed to achieve the optimal synergy between CT/RT and innate as well as adaptive immunity in the treatment of cancer.

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Section: The Effect Of Ct/rt On Hla Molecule Expressionmentioning

confidence: 96%

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

Rosental¹,

Appel²,

Yossef³

et al. 2012

CMC

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“…These include epigenetic mechanisms, like CpG methylation and histone deacetylation [70, 106], or not yet identified factors, which negatively interfere with HLA-G expression [96]. So far, HLA-G methylation has been found not only in solid tumors, such as lung, colon, ovarian carcinoma and RCC, but also in hematopoietic malignancies [55, 70, 106–108]. The level of HLA-G promoter methylation significantly differed in the tumor cells analyzed, as demonstrated by methylation-specific PCR, bisulfite sequencing as well as by combined bisulfite restriction analysis (COBRA).…”

Section: Molecular Mechanisms Involved In Impaired Hla-g Expressionmentioning

confidence: 99%

“…The level of HLA-G promoter methylation significantly differed in the tumor cells analyzed, as demonstrated by methylation-specific PCR, bisulfite sequencing as well as by combined bisulfite restriction analysis (COBRA). Treatment of HLA-G- tumor cells with 5-aza-2-desoxycytidine (DAC) reversed HLA-G repression by demethylation of the HLA-G promoter, which enhanced HLA-G transcription and protein expression in some leukemia and solid tumor cells [70, 108], but only rarely induced HLA-G [55, 109]. In normal non-malignant tissues and cell lines, HLA-G methylation has either not been demonstrated or only detected at a low frequency [55, 107].…”

Section: Molecular Mechanisms Involved In Impaired Hla-g Expressionmentioning

confidence: 99%

Biology of HLA-G in cancer: a candidate molecule for therapeutic intervention?

Amiot

Ferrone

Grosse‐Wilde

et al. 2010

Cell. Mol. Life Sci.

119

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Although the expression of the non-classical HLA class I molecule HLA-G was first reported to be restricted to the fetal–maternal interface on the extravillous cytotrophoblasts, the distribution of HLA-G in normal tissues appears broader than originally described. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. More interestingly, under pathophysiological conditions HLA-G antigens may be expressed on various types of malignant cells suggesting that HLA-G antigen expression is one strategy used by tumor cells to escape immune surveillance. In this article, we will focus on HLA-G expression in cancers of distinct histology and its association with the clinical course of diseases, on the underlying molecular mechanisms of impaired HLA-G expression, on the immune tolerant function of HLA-G in tumors, and on the use of membrane-bound and soluble HLA-G as a diagnostic or prognostic biomarker to identify tumors and to monitor disease stage, as well as on the use of HLA-G as a novel therapeutic target in cancer.

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“…Treatment of a HLA-G-negative melanoma cell line with 5azaC restored HLA-G expression; similarly 5azaC activated HLA-G expression in human leukemia cell lines, even in malignant hematopoietic cells isolated from patients with acute myeloid leukemia (AML) and chronic lymphocytic leukemia (B-CLL) (Polakova et al, 2009a;Polakova et al, 2009b). Further research found that HLA-G was silenced as a result of CpG hypermethylation within a 5′ regulatory region upstream of the start codon (Moreau et al, 2003;Yan et al, 2005).…”

Section: Hla-ligand Of Kirmentioning

confidence: 99%

Transcription Regulation and Epigenetic Control of Expression of Natural Killer Cell Receptors and Their Ligands

Zhou¹,

Zhang²,

Zhang³

et al. 2011

Advances in Cancer Therapy

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Activation of HLA-G expression by 5-aza-2´- deoxycytidine in malignant hematopoetic cells isolated from leukemia patients

Cited by 16 publications

References 30 publications

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells

Biology of HLA-G in cancer: a candidate molecule for therapeutic intervention?

Transcription Regulation and Epigenetic Control of Expression of Natural Killer Cell Receptors and Their Ligands

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