Hypermethylation of IFN-γ in oral cancer tissues

Tian, Shaomin; Jiang, Chunyang; Liu, Xiaoqin; Xu, Sheng; Zhang, Zhiyong; Chen, Huizhen; Zhang, Yinghuai; Liu, Yanping; Ma, Dong

doi:10.1007/s00784-017-2052-z

Cited by 14 publications

(9 citation statements)

References 21 publications

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“…The killing effects of the purified T cells in the mice vaccinated with DRibble-DCs were significantly higher than those in the mice immunized with PBS. The secretion of IFN-γ, an important tumor suppressor, 23 in the T-cell culture supernatants incubated with SCC7 cells was consistent with the results obtained in the target-cell killing assay, which is a direct measure of the immune response in vaccine-immunized mice. IFN-γ is a recognized indicator of antitumor immunity; thus, the percentages of CD3 + CD4 + IFN-γ + T cells (helper T cells) and CD3 + CD8 + IFN-γ + T cells (cytotoxic T cells) in lymphoid organs and peripheral blood reflect the antitumor immunity of vaccines.…”

Section: Discussionsupporting

confidence: 85%

Immunocompetence and mechanism of the DRibble-DCs vaccine for oral squamous cell carcinoma

Dong¹,

Su²,

Chen³

et al. 2018

CMAR

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BackgroundDue to the high-quality immunogenicity of tumor-derived autophagosomes (DRibbles), we aimed to explore the antitumor ability and mechanism of DRibble-loaded dendritic cells (DRibble-DCs).Materials and methodsDRibbles extracted from the oral squamous cell carcinoma cell line SCC7 express specific LC3-II and ubiquitination marker. Immunization of mice with the DRibble-DCs vaccine led to the proliferation and differentiation of CD3+CD4+IFN-γ+ and CD3+CD8+IFN-γ+ T cells. The expression of proteins in endoplasmic reticulum stress (ERS) pathways was determined by Western blotting. Additionally, the functional properties of the DRibble-DCs were examined in mice, and regulatory T cells were measured by flow cytometry.ResultsExcellent biocompatibility was observed in vitro when DCs were loaded with DRibbles. T cells of lymph nodes and spleens from mice immunized with DRibble-DCs had cytotoxic effects on SCC7 cells. DCs homeostasis and ERS-related proteins were affected by DRibbles. Moreover, the DRibble-DCs vaccine achieved significantly better antitumor efficacy than DRibbles and tumor cell lysate-loaded DCs.ConclusionThe results validated the antitumor immune responses to the DRibble-DCs vaccine in vivo and in vitro. The ERS pathway can be affected by DRibbles.

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Section: Discussionsupporting

confidence: 85%

Immunocompetence and mechanism of the DRibble-DCs vaccine for oral squamous cell carcinoma

Dong¹,

Su²,

Chen³

et al. 2018

CMAR

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“…The present data provide associative evidence for the involvement of gene hypermethylation in the suppression of Ifn-ɣ mRNA expression in fetal alcohol-exposed rats. Previous studies have shown a similar inverse association between Ifn-ɣ gene methylation and Ifn-ɣ mRNA expression in oral cancer as well as in vitamin D treatment during fetal growth [37,38]. Furthermore, it has been shown that demethylation of some of the CpG sites in the promoter of the Ifn-ɣ gene increases mRNA expression in CD44(high)CD8+ T cells [39].…”

Section: Discussionmentioning

confidence: 67%

Transgenerational inheritance of fetal alcohol exposure adverse effects on immune gene interferon-ϒ

2020

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Background: Alcohol exposures in utero have been shown to alter immune system functions in the offspring which persists into adulthood. However, it is not apparent why the in utero alcohol effect on the immune system persists into adulthood of fetal alcohol-exposed offspring. The objective of this study was to determine the longterm effects of fetal alcohol exposure on the production of interferon-ϒ (IFN-ϒ), a cytokine known to regulate both innate and adaptive immunity. Methods: Isogenic Fisher 344 rats were bred to produce pregnant dams, which were fed with a liquid diet containing 6.7% alcohol between gestation days 7 and 21 and pair-fed with an isocaloric liquid diet or fed ad libitum with rat chow; their male and female offspring were used for the study. F1-F3 generation rats were used when they were 2 to 3 months old. Fetal alcohol exposure effects on the Ifn-ɣ gene was determined by measuring the gene promoter methylation and mRNA and protein expression in the spleen. Additionally, transgenerational studies were conducted to evaluate the germline-transmitted effects of fetal alcohol exposure on the Ifn-ɣ gene. Results: Fetal alcohol exposure reduced the expression of Ifn-ɣ mRNA and IFN-ϒ protein while it increased the proximal promoter methylation of the Ifn-ɣ gene in both male and female offspring during the adult period. Transgenerational studies revealed that the reduced levels of Ifn-ɣ expression and increased levels of its promoter methylation persisted only in F2 and F3 generation males derived from the male germ line. Conclusion: Overall, these findings provide the evidence that fetal alcohol exposures produce an epigenetic mark on the Ifn-ɣ gene that passes through multiple generations via the male germ line. These data provide the first evidence that the male germ line transmits fetal alcohol exposure's adverse effects on the immune system.

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“…The other type of cytokine identified in this study is IFNγ . In oral epithelial cells, a loss of IFNγ expression may be caused by the IFN-γ promoter methylation as a plausible underlying mechanism for oral cancer progression [ 86 ]. Furthermore, and in concordance with our data, low IFNγ levels are associated with poor prognosis in HNSCC including oral [ 87 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis

López-Ozuna

Gupta

Kiow

et al. 2020

Toxics

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Water-pipe smoking (WPS) is becoming the most popular form of tobacco use among the youth, especially in the Middle East, replacing cigarettes rapidly and becoming a major risk of tobacco addiction worldwide. Smoke from WPS contains similar toxins as those present in cigarette smoke and is linked directly with different types of cancers including lung and head and neck (HN) carcinomas. However, the underlying molecular pathways and/or target genes responsible for the carcinogenic process are still unknown. In this study, human normal oral epithelial (HNOE) cells, NanoString PanCancer Pathways panel of 770 gene transcripts and quantitative real-time polymerase chain reaction (qRT-PCR) analysis were applied to discover differentially expressed genes (DEG) modulated by WPS. In silico analysis was performed to analyze the impact of these genes in HN cancer patient’s biology and outcome. We found that WPS can induce the epithelial–mesenchymal transition (EMT: hallmark of cancer progression) of HNOE cells. More significantly, our analysis of NanoString revealed 23 genes deregulated under the effect of WPS, responsible for the modulation of cell cycle, proliferation, migration/invasion, apoptosis, signal transduction, and inflammatory response. Further analysis was performed using qRT-PCR of HNOE WPS-exposed and unexposed cells supported the reliability of our NanoString data. Moreover, we demonstrate those DEG to be upregulated in cancer compared with normal tissue. Using the Kaplan–Meier analysis, we observed a significant association between WPS-deregulated genes and relapse-free survival/overall survival in HN cancer patients. Our findings imply that WPS can modulate EMT as well as a set of genes that are directly involved in human HN carcinogenesis, thereby affecting HN cancer patients’ survival.

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Hypermethylation of IFN-γ in oral cancer tissues

Abstract: IFN-γ hypermethylation during the process of oral carcinogenesis could be useful for the clinical diagnosis and treatment for OSCC.

Cited by 14 publications

References 21 publications

Immunocompetence and mechanism of the DRibble-DCs vaccine for oral squamous cell carcinoma

Immunocompetence and mechanism of the DRibble-DCs vaccine for oral squamous cell carcinoma

Transgenerational inheritance of fetal alcohol exposure adverse effects on immune gene interferon-ϒ

Water-Pipe Smoking Exposure Deregulates a Set of Genes Associated with Human Head and Neck Cancer Development and Prognosis

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