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DNA methylation cancer immune response

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https://www.readbyqxmd.com/read/28074529/epigenetic-mediated-immune-suppression-of-positive-co-stimulatory-molecules-in-chemoresistant-ovarian-cancer-cells
#1
Ercan Cacan
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Ovarian cancer creates a suppressive microenvironment to escape immune elimination; however, the molecular mechanisms are poorly understood, and it is unclear whether chemotherapeutic drugs exert an immunoreactive or immunosuppressive effect on the tumor microenvironment. 4-1BB ligand (4-1BBL/CD157) and OX-40 ligand (OX-40L/CD252) are important regulators of effector cytotoxic T-cells activity...
January 11, 2017: Cell Biology International
https://www.readbyqxmd.com/read/28057213/a-new-molecular-mechanism-underlying-the-antitumor-effect-of-dna-methylation-inhibitors-via-an-antiviral-immune-response
#2
Y Saito, T Nakaoka, H Saito
Chromatin remodeling mediated by DNA methylation and histone modifications play critical roles in the transcriptional regulation of protein-coding genes, noncoding RNAs such as microRNAs, and endogenous retroviruses (ERVs). Many studies have shown that aberrant DNA methylation and histone modifications are associated with the initiation and progression of various malignancies. Epigenetic silencing of tumor suppressor genes in cancer is generally mediated by DNA hypermethylation of CpG island promoters and histone modifications such as histone deacetylation, methylation of histone H3 lysine 9 (H3K9), and trimethylation of H3K27...
2017: Advances in Protein Chemistry and Structural Biology
https://www.readbyqxmd.com/read/27982729/differential-dna-methylation-and-pm2-5-species-in-a-450k-epigenome-wide-association-study
#3
Lingzhen Dai, Amar Mehta, Irina Mordukhovich, Allan C Just, Jincheng Shen, Lifang Hou, Petros Koutrakis, David Sparrow, Pantel S Vokonas, Andrea A Baccarelli, Joel D Schwartz
Although there is growing evidence that exposure to ambient particulate matter is associated with global DNA methylation and gene-specific methylation, little is known regarding epigenome-wide changes in DNA methylation in relation to particles and, especially, particle components. Using the Illumina Infinium HumanMethylation450 BeadChip, we examined the relationship between one-year moving averages of PM2.5 species (Al, Ca, Cu, Fe, K, Na, Ni, S, Si, V, and Zn) and DNA methylation at 484,613 CpG probes in a longitudinal cohort that included 646 subjects...
December 16, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27959926/predictors-of-chemosensitivity-in-triple-negative-breast-cancer-an-integrated-genomic-analysis
#4
Tingting Jiang, Weiwei Shi, Vikram B Wali, Lőrinc S Pongor, Charles Li, Rosanna Lau, Balázs Győrffy, Richard P Lifton, William F Symmans, Lajos Pusztai, Christos Hatzis
BACKGROUND: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients. METHODS AND FINDINGS: We performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) selected because they had either pCR (n = 18) or extensive residual disease (n = 11) after neoadjuvant chemotherapy, with cases from The Cancer Genome Atlas (TCGA; n = 144) and METABRIC (n = 278) cohorts serving as validation cohorts...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/27865469/interplay-between-inflammation-and-epigenetic-changes-in-cancer
#5
A R Maiuri, H M O'Hagan
Immune responses can suppress tumorigenesis, but also contribute to cancer initiation and progression suggesting a complex interaction between the immune system and cancer. Epigenetic alterations, which are heritable changes in gene expression without changes to the DNA sequence, also play a role in carcinogenesis through silencing expression of tumor suppressor genes and activating oncogenic signaling. Interestingly, epithelial cells at sites of chronic inflammation undergo DNA methylation alterations that are similar to those present in cancer cells, suggesting that inflammation may initiate cancer-specific epigenetic changes in epithelial cells...
2016: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/27863190/human-papillomavirus-drives-tumor-development-throughout-the-head-and-neck-improved-prognosis-is-associated-with-an-immune-response-largely-restricted-to-the-oropharynx
#6
Ankur Chakravarthy, Stephen Henderson, Stephen M Thirdborough, Christian H Ottensmeier, Xiaoping Su, Matt Lechner, Andrew Feber, Gareth J Thomas, Tim R Fenton
Purpose In squamous cell carcinomas of the head and neck (HNSCC), the increasing incidence of oropharyngeal squamous cell carcinomas (OPSCCs) is attributable to human papillomavirus (HPV) infection. Despite commonly presenting at late stage, HPV-driven OPSCCs are associated with improved prognosis compared with HPV-negative disease. HPV DNA is also detectable in nonoropharyngeal (non-OPSCC), but its pathogenic role and clinical significance are unclear. The objectives of this study were to determine whether HPV plays a causal role in non-OPSCC and to investigate whether HPV confers a survival benefit in these tumors...
December 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/27835705/dna-methylation-mediated-downregulation-of-defb1-in-prostate-cancer-cells
#7
Jaehyouk Lee, Jun Hyun Han, Ara Jang, Jin Wook Kim, Soon Auck Hong, Soon Chul Myung
Epigenetic aberrations play crucial roles in prostate cancer (PCa) development and progression. The DEFB1 gene, which encodes human ß-defensin-1 (HBD-1), contributes to innate immune responses and functions as a potential tumor suppressor in urological cancers. We investigated whether differential DNA methylation at the low CpG-content promoter (LCP) of DEFB1 was associated with transcriptional regulation of DEFB1 in PCa cells. To identify distinct CpG loci within the DEFB1 LCP related to the epigenetic regulation of DEFB1, we performed an in vitro methylated reporter assay followed by bisulfite sequencing of the DEFB1 promoter fragment...
2016: PloS One
https://www.readbyqxmd.com/read/27826838/the-role-of-dna-methylation-in-cancer
#8
Ranjani Lakshminarasimhan, Gangning Liang
The malignant transformation of normal cells is driven by both genetic and epigenetic changes. With the advent of next-generation sequencing and large-scale multinational consortium studies, it has become possible to profile the genomes and epigenomes of thousands of primary tumors from nearly every cancer type. From these genome-wide studies, it became clear that the dynamic regulation of DNA methylation is a critical epigenetic mechanism of cancer initiation, maintenance, and progression. Proper control of DNA methylation is not only crucial for regulating gene transcription, but its broader consequences include maintaining the integrity of the genome and modulating immune response...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27814656/alpha-enolase-eno1-a-potential-target-in-novel-immunotherapies
#9
Paola Cappello, Moitza Principe, Sara Bulfamante, Francesco Novelli
Alpha-enolase (ENO1) is a metabolic enzyme involved in the synthesis of pyruvate. It also acts as a plasminogen receptor and mediates the activation of plasmin and extracellular matrix degradation. In tumor cells, ENO1 is up-regulated and supports the Warburg effect; it is expressed at the cell surface, where it promotes cancer invasion, and is subjected to a specific array of post-translational modifications, namely acetylation, methylation and phosphorylation. ENO1 overexpression and post-translational modifications could be of diagnostic and prognostic value in many cancer types...
January 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/27770445/understanding-the-epigenetic-regulation-of-tumours-and-their-microenvironments-opportunities-and-problems-for-epigenetic-therapy
#10
REVIEW
Man Liu, Jingying Zhou, Zhiwei Chen, Alfred Sze-Lok Cheng
The tumour microenvironment plays an instrumental role in cancer development, progression and treatment response/resistance. Accumulating evidence is underscoring the fundamental importance of epigenetic regulation in tumour immune evasion. Following many pioneering discoveries demonstrating malignant transformation through epigenetic anomalies ('epimutations'), there is also a growing emphasis on elucidating aberrant epigenetic mechanisms that reprogramme the milieu of tumour-associated immune and stromal cells towards an immunosuppressive state...
January 2017: Journal of Pathology
https://www.readbyqxmd.com/read/27700179/epigenetic-control-of-the-tumor-microenvironment
#11
David L Marks, Rachel Lo Olson, Martin E Fernandez-Zapico
Stromal cells of the tumor microenvironment have been shown to play important roles in both supporting and limiting cancer growth. The altered phenotype of tumor-associated stromal cells (fibroblasts, immune cells, endothelial cells etc.) is proposed to be mainly due to epigenetic dysregulation of gene expression; however, only limited studies have probed the roles of epigenetic mechanisms in the regulation of stromal cell function. We review recent studies demonstrating how specific epigenetic mechanisms (DNA methylation and histone post-translational modification-based gene expression regulation, and miRNA-mediated translational regulation) drive aspects of stromal cell phenotype, and discuss the implications of these findings for treatment of malignancies...
December 2016: Epigenomics
https://www.readbyqxmd.com/read/27672289/therapeutic-aspects-of-c-myc-signaling-in-inflammatory-and-cancerous-colonic-diseases
#12
REVIEW
Ferenc Sipos, Gábor Firneisz, Györgyi Műzes
Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation...
September 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27635108/expression-of-cancer-testis-antigens-in-colorectal-cancer-new-prognostic-and-therapeutic-implications
#13
Maciej Tarnowski, Michał Czerewaty, Anna Deskur, Krzysztof Safranow, Wojciech Marlicz, Elżbieta Urasińska, Mariusz Z Ratajczak, Teresa Starzyńska
Background. While cancer/testis antigens (CTAs) are restricted in postnatal tissues to testes and germ line-derived cells, their role in cancer development and the clinical significance of their expression still remain to be better defined. Objective. The aim of this study was to investigate the level of CTA expression in colon samples from patients with colorectal cancer (CRC) in relation to patient clinical status. Methods. Forty-five patients with newly diagnosed colorectal cancer were included in the study...
2016: Disease Markers
https://www.readbyqxmd.com/read/27633916/an-integrative-and-comparative-study-of-pan-cancer-transcriptomes-reveals-distinct-cancer-common-and-specific-signatures
#14
Zhen Cao, Shihua Zhang
To investigate the commonalities and specificities across tumor lineages, we perform a systematic pan-cancer transcriptomic study across 6744 specimens. We find six pan-cancer subnetwork signatures which relate to cell cycle, immune response, Sp1 regulation, collagen, muscle system and angiogenesis. Moreover, four pan-cancer subnetwork signatures demonstrate strong prognostic potential. We also characterize 16 cancer type-specific subnetwork signatures which show diverse implications to somatic mutations, somatic copy number aberrations, DNA methylation alterations and clinical outcomes...
September 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27577073/hypoxia-inducible-factor-1-mediates-the-expression-of-the-immune-checkpoint-hla-g-in-glioma-cells-through-hypoxia-response-element-located-in-exon-2
#15
Layale Yaghi, Isabelle Poras, Renata T Simoes, Eduardo A Donadi, Jörg Tost, Antoine Daunay, Bibiana Sgorla de Almeida, Edgardo D Carosella, Philippe Moreau
HLA-G is an immune checkpoint molecule with specific relevance in cancer immunotherapy. It was first identified in cytotrophoblasts, protecting the fetus from maternal rejection. HLA-G tissue expression is very restricted but induced in numerous malignant tumors such as glioblastoma, contributing to their immune escape. Hypoxia occurs during placenta and tumor development and was shown to activate HLA-G. We aimed to elucidate the mechanisms of HLA-G activation under conditions combining hypoxia-mimicking treatment and 5-aza-2'deoxycytidine, a DNA demethylating agent used in anti-cancer therapy which also induces HLA-G...
September 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27467919/unraveling-the-molecular-pathways-of-dna-methylation-inhibitors-human-endogenous-retroviruses-induce-the-innate-immune-response-in-tumors
#16
Reiner Strick, Pamela L Strissel, Stephen B Baylin, Katherine B Chiappinelli
Loss of DNA methylation can activate endogenous retroviral expression and dsRNA in cancer cells. This leads to induction of toll-like receptor signaling stimulating an antiviral interferon response. Recent findings provide a therapeutic rationale for combining DNA methylation inhibitors with blockage of immune checkpoint proteins to fight cancer.
May 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27386846/expression-and-methylation-patterns-partition-luminal-a-breast-tumors-into-distinct-prognostic-subgroups
#17
Dvir Netanely, Ayelet Avraham, Adit Ben-Baruch, Ella Evron, Ron Shamir
BACKGROUND: Breast cancer is a heterogeneous disease comprising several biologically different types, exhibiting diverse responses to treatment. In the past years, gene expression profiling has led to definition of several "intrinsic subtypes" of breast cancer (basal-like, HER2-enriched, luminal-A, luminal-B and normal-like), and microarray based predictors such as PAM50 have been developed. Despite their advantage over traditional histopathological classification, precise identification of breast cancer subtypes, especially within the largest and highly variable luminal-A class, remains a challenge...
July 7, 2016: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/27143627/inhibition-of-dna-methylation-suppresses-intestinal-tumor-organoids-by-inducing-an-anti-viral-response
#18
Yoshimasa Saito, Toshiaki Nakaoka, Kasumi Sakai, Toshihide Muramatsu, Kohta Toshimitsu, Masaki Kimura, Takanori Kanai, Toshiro Sato, Hidetsugu Saito
Recent studies have proposed that the major anti-tumor effect of DNA methylation inhibitors is induction of interferon-responsive genes via dsRNAs-containing endogenous retroviruses. Recently, a 3D culture system for stem cells known as organoid culture has been developed. Lgr5-positive stem cells form organoids that closely recapitulate the properties of original tissues. To investigate the effect of DNA demethylation on tumor organoids, we have established organoids from intestinal tumors of Apc(Min/+) (Min) mice and subjected them to 5-aza-2'-deoxycytidine (5-Aza-CdR) treatment and Dnmt1 knockdown...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27115166/systematic-study-of-novel-lncrnas-in-different-gastrointestinal-cancer-cells
#19
Baoping Cao, Nanxi Song, Meiying Zhang, Chao Di, Yang Yang, Youyong Lu, Runsheng Chen, Zhi John Lu, Mingzhou Guo
BACKGROUND: Recently, many lncRNAs were found to be deregulated in various human cancers and play important roles in carcinogenesis. MATERIAL AND METHODS: To investigate the association of lncRNAs to gastrointestinal cancers, 12 cases of esophageal cancer and hepatic cancer, 16 cases of gastric cancer and colorectal cancer and their matched adjacent tissue samples, 12 esophageal cancer cell lines, 7 gastric cancer cell lines, 10 colorectal cancer cell lines, and 11 hepatic cancer cell lines were examined...
March 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27112593/genome-wide-non-cpg-methylation-of-the-host-genome-during-m-tuberculosis-infection
#20
Garima Sharma, Divya Tej Sowpati, Prakruti Singh, Mehak Zahoor Khan, Rakesh Ganji, Sandeep Upadhyay, Sharmistha Banerjee, Vinay Kumar Nandicoori, Sanjeev Khosla
A mammalian cell utilizes DNA methylation to modulate gene expression in response to environmental changes during development and differentiation. Aberrant DNA methylation changes as a correlate to diseased states like cancer, neurodegenerative conditions and cardiovascular diseases have been documented. Here we show genome-wide DNA methylation changes in macrophages infected with the pathogen M. tuberculosis. Majority of the affected genomic loci were hypermethylated in M. tuberculosis infected THP1 macrophages...
2016: Scientific Reports
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