scholarly journals Epigenetic regulation of cancer biology and anti-tumor immunity by EZH2

Oncotarget ◽  
2016 ◽  
Vol 7 (51) ◽  
pp. 85624-85640 ◽  
Author(s):  
Anthos Christofides ◽  
Theodoros Karantanos ◽  
Kankana Bardhan ◽  
Vassiliki A. Boussiotis
2020 ◽  
Author(s):  
Shanmei Jiang ◽  
Yin He ◽  
Mengyuan Li ◽  
Xiaosheng Wang

Abstract Objectives The cell cycle pathway regulating cell proliferation is overactivated in various cancers. Immune evasion is another important mechanism for tumor cell hyperproliferation. Nevertheless, the relationship between cell cycle and tumor immunity remains not fully understood. Materials and Methods Using the cancer genomics datasets for 10 cancer cohorts from the Cancer Genome Atlas (TCGA) program, we investigated the association between cell cycle activity (CCA) and anti-tumor immune signatures. We also explored the association between CCA and PD-L1 expression in these cancer cohorts. Moreover, we investigated the association between CCA and immunotherapy response in several cancer cohorts receiving immunotherapy. Results CCA likely exhibited positive associations with anti-tumor immune signatures (CD8+ T cell infiltration and immune cytolytic activity) in these cancer cohorts. The strong positive associations of CCA with DNA damage repair pathways and with tumor mutation load may explain the positive associations between CCA and anti-tumor immune signatures. Moreover, CCA displayed significant positive correlations with PD-L1 expression. Finally, we found that the enhanced CCA tended to be associated with unfavorable clinical outcomes in the TCGA cancer cohorts, though such association was not observed in the cancer cohorts receiving immune checkpoint blockade therapy. Conclusions CCA has significant positive associations with both anti-tumor immune signatures and tumor immune-suppressive signatures in diverse cancer types. Our findings provide new insights into cancer biology and potential clinical implications for cancer immunotherapy.


Impact ◽  
2021 ◽  
Vol 2021 (8) ◽  
pp. 9-11
Author(s):  
Tsuyoshi Osawa

New approaches for treating cancers are required and advances in 'omics' technologies including genomics, epigenomics, transcriptomics could provide valuable treatment options. Associate Professor Tsuyoshi Osawa, Research Center for Advanced Science and Technology (RCAST), University of Tokyo, believes that integrative techniques are essential in combating cancer. Osawa's lab is utilising a pioneering approach called nutriomics that involves applying multiple omics technologies to cancer biology. These omics approaches can be used to generate detailed genetic and molecular profiles of whole tumours, allowing researchers to discover important information about the tumour cells. In addition, they provide an opportunity to explore the healthy cells surrounding the tumour, thereby establishing a picture of the interactions between the tumour and the microenvironment in which it exists, which is important information that could be exploited for treatments methods. Using the omics approach, the researchers have been able to identify and describe the functions of the metabolites contributing to the malignant progression of cancer cells. They found that hypoxia, nutrient starvation and acidic pH all induce tumour aggressiveness by epigenetic regulation. Osawa and the team now want to identify further cancer metabolites that lead to malignancy and, ultimately, develop therapeutics for metastasis and recurrent advanced cancer from the viewpoint of an integrative multiomics approach.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Graeme Greenfield ◽  
Mary Frances McMullin ◽  
Ken Mills

AbstractThe Philadelphia negative myeloproliferative neoplasms (MPN) compromise a heterogeneous group of clonal myeloid stem cell disorders comprising polycythaemia vera, essential thrombocythaemia and primary myelofibrosis. Despite distinct clinical entities, these disorders are linked by morphological similarities and propensity to thrombotic complications and leukaemic transformation. Current therapeutic options are limited in disease-modifying activity with a focus on the prevention of thrombus formation. Constitutive activation of the JAK/STAT signalling pathway is a hallmark of pathogenesis across the disease spectrum with driving mutations in JAK2, CALR and MPL identified in the majority of patients. Co-occurring somatic mutations in genes associated with epigenetic regulation, transcriptional control and splicing of RNA are variably but recurrently identified across the MPN disease spectrum, whilst epigenetic contributors to disease are increasingly recognised. The prognostic implications of one MPN diagnosis may significantly limit life expectancy, whilst another may have limited impact depending on the disease phenotype, genotype and other external factors. The genetic and clinical similarities and differences in these disorders have provided a unique opportunity to understand the relative contributions to MPN, myeloid and cancer biology generally from specific genetic and epigenetic changes. This review provides a comprehensive overview of the molecular pathophysiology of MPN exploring the role of driver mutations, co-occurring mutations, dysregulation of intrinsic cell signalling, epigenetic regulation and genetic predisposing factors highlighting important areas for future consideration.


2021 ◽  
Vol 12 ◽  
Author(s):  
Junwei Liu ◽  
Saisi Qu ◽  
Tongtong Zhang ◽  
Yufei Gao ◽  
Hongyu Shi ◽  
...  

The tumor microenvironment (TME) is an ecosystem that contains various cell types, including cancer cells, immune cells, stromal cells, and many others. In the TME, cancer cells aggressively proliferate, evolve, transmigrate to the circulation system and other organs, and frequently communicate with adjacent immune cells to suppress local tumor immunity. It is essential to delineate this ecosystem’s complex cellular compositions and their dynamic intercellular interactions to understand cancer biology and tumor immunology and to benefit tumor immunotherapy. But technically, this is extremely challenging due to the high complexities of the TME. The rapid developments of single-cell techniques provide us powerful means to systemically profile the multiple omics status of the TME at a single-cell resolution, shedding light on the pathogenic mechanisms of cancers and dysfunctions of tumor immunity in an unprecedently resolution. Furthermore, more advanced techniques have been developed to simultaneously characterize multi-omics and even spatial information at the single-cell level, helping us reveal the phenotypes and functionalities of disease-specific cell populations more comprehensively. Meanwhile, the connections between single-cell data and clinical characteristics are also intensively interrogated to achieve better clinical diagnosis and prognosis. In this review, we summarize recent progress in single-cell techniques, discuss their technical advantages, limitations, and applications, particularly in tumor biology and immunology, aiming to promote the research of cancer pathogenesis, clinically relevant cancer diagnosis, prognosis, and immunotherapy design with the help of single-cell techniques.


Author(s):  
Renato Paro ◽  
Ueli Grossniklaus ◽  
Raffaella Santoro ◽  
Anton Wutz

AbstractMost chromatin-modifying enzymes use metabolites as cofactors. Consequently, the cellular metabolism can influence the capacity of the cell to write or erase chromatin marks. This points to an intimate relationship between metabolic and epigenetic regulation. In this chapter, we describe the biosynthetic pathways of cofactors that are implicated in epigenetic and chromatin regulation and provide examples of how metabolic pathways can influence chromatin and epigenetic processes as well as their interplay in developmental and cancer biology.


2012 ◽  
Vol 90 (7) ◽  
pp. 791-801 ◽  
Author(s):  
Lilian E. van Vlerken ◽  
Elaine M. Hurt ◽  
Robert E. Hollingsworth

Author(s):  
Alan P. Koretsky ◽  
Afonso Costa e Silva ◽  
Yi-Jen Lin

Magnetic resonance imaging (MRI) has become established as an important imaging modality for the clinical management of disease. This is primarily due to the great tissue contrast inherent in magnetic resonance images of normal and diseased organs. Due to the wide availability of high field magnets and the ability to generate large and rapidly switched magnetic field gradients there is growing interest in applying high resolution MRI to obtain microscopic information. This symposium on MRI microscopy highlights new developments that are leading to increased resolution. The application of high resolution MRI to significant problems in developmental biology and cancer biology will illustrate the potential of these techniques.In combination with a growing interest in obtaining high resolution MRI there is also a growing interest in obtaining functional information from MRI. The great success of MRI in clinical applications is due to the inherent contrast obtained from different tissues leading to anatomical information.


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