EZH2 as a Regulator of CD8+ T Cell Fate and Function

Stairiker, Christopher J.; Thomas, Graham D.; Salek-Ardakani, Shahram

doi:10.3389/fimmu.2020.593203

Cited by 31 publications

(37 citation statements)

References 64 publications

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“…Increased glycolysis and β-oxidation in immune cells lead to elevated intracellular levels of Ac-CoA, which, when used as a group donor by HATs, causes a relaxed, more transcriptionally active chromatin state [53]. Moreover, EZH2 epigenetically regulates T-cell differentiation and Treg cell function, and its modulation in T cells was shown to improve the efficacy of immune checkpoint therapy (ICT) [56][57][58].…”

Section: Adaptive Immune Cells: T Cells and B Cellsmentioning

confidence: 99%

Regulation of antitumor immunity by inflammation-induced epigenetic alterations

Karin

Shalapour

2021

Cell Mol Immunol

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Chronic inflammation promotes tumor development, progression, and metastatic dissemination and causes treatment resistance. The accumulation of genetic alterations and loss of normal cellular regulatory processes are not only associated with cancer growth and progression but also result in the expression of tumor-specific and tumor-associated antigens that may activate antitumor immunity. This antagonism between inflammation and immunity and the ability of cancer cells to avoid immune detection affect the course of cancer development and treatment outcomes. While inflammation, particularly acute inflammation, supports T-cell priming, activation, and infiltration into infected tissues, chronic inflammation is mostly immunosuppressive. However, the main mechanisms that dictate the outcome of the inflammation-immunity interplay are not well understood. Recent data suggest that inflammation triggers epigenetic alterations in cancer cells and components of the tumor microenvironment. These alterations can affect and modulate numerous aspects of cancer development, including tumor growth, the metabolic state, metastatic spread, immune escape, and immunosuppressive or immunosupportive leukocyte generation. In this review, we discuss the role of inflammation in initiating epigenetic alterations in immune cells, cancer-associated fibroblasts, and cancer cells and suggest how and when epigenetic interventions can be combined with immunotherapies to improve therapeutic outcomes.

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Section: Adaptive Immune Cells: T Cells and B Cellsmentioning

confidence: 99%

Regulation of antitumor immunity by inflammation-induced epigenetic alterations

Karin

Shalapour

2021

Cell Mol Immunol

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“…36 It should be noted that EZH2 is also expressed in T cells, playing an important role in the differentiation, lineage maintenance, and anti-tumor activity of these cells. 37 Clearly, EZH2 plays a crucial role in FL biology by blocking the exit of B cells from GCs and by remodeling their environment. Genetic alterations of its gene increase the EZH2-dependency of tumor cells.…”

Section: The Role Of Ezh2 In Normal and Malignant B-cells And Their Microenvironmentsmentioning

confidence: 99%

“…36 It should be noted that EZH2 is also expressed in T cells, playing an important role in the differentiation, lineage maintenance, and anti-tumor activity of these cells. 37…”

Section: The Role Of Ezh2 In Normal and Malignant B-cells And Their Microenvironmentsmentioning

confidence: 99%

The role of tazemetostat in relapsed/refractory follicular lymphoma

Keudell

Salles

2021

Therapeutic Advances in Hematology

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Large strides have been made in the treatment of follicular lymphoma (FL) over the last few years. Although the majority of patients respond to upfront therapy, many experience disease progression with a progressive shortening of subsequent treatment free intervals. New treatment options are therefore crucial for such patients. Tazemetostat is a first-in-class, selective, oral inhibitor of enhancer of zester homolog 2 (EZH2), a histone methyltransferase that is mutated in about a quarter of FL cases. Tazemetostat was recently approved for the treatment of patients with relapsed FL after 2 or more prior lines of therapy in the presence of an EZH2 mutation and for those without any other available therapeutic option, independently of EZH2 mutation status. In this review, we will summarize the background and key data that led to the development of tazemetostat, and, ultimately, to its approval for this indication.

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“…PRC2/EZH2 has been shown to be involved in normal haematopoiesis, the regulation of immune cells, and is essential for T-cell proliferation and anti-tumour immunity [73][74][75][76] . Conversely it is also implicated in some haematological malignancies [77,78] .…”

Section: The Mechanism Of Action Of Ezh2 In Stsmentioning

confidence: 99%

Targeting EZH2 for the treatment of soft tissue sarcomas

Karolak¹,

Tracy²,

Shipley³

et al. 2021

JCMT

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Soft tissue sarcomas (STS) are a heterogenous group of rare malignancies of mesenchymal origin, affecting both children and adults. The majority of STS have a poor prognosis and advanced stage at the time of diagnosis. Standard treatments for STS largely constitute tumour resection with chemotherapy and/or radiotherapy, and there has been little significant advancement in the application of novel therapies for treatment of these tumours. The current multimodal approach to therapy often leads to long-term side effects, and for some patients, resistance to cytotoxic agents is associated with local recurrence and/or metastasis. There is, therefore, a need for novel therapeutic strategies for the treatment of STS. Recent advances in epigenetics have implicated the histone methyltransferase, EZH2, in the development and progression of diseases such as breast cancer, lymphoma and more recently STS. Here we will review the current literature for EZH2 in STS, including high expression of EZH2 in STS and correlation of this with specific features of malignancy (metastasis, histological grade, and prognosis). The effects of targeting EZH2 using RNA interference and small molecule inhibitors will also be reviewed and the potential for the use of EZH2 inhibition in therapeutic strategies for STS patients will be discussed.

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EZH2 as a Regulator of CD8+ T Cell Fate and Function

Cited by 31 publications

References 64 publications

Regulation of antitumor immunity by inflammation-induced epigenetic alterations

Regulation of antitumor immunity by inflammation-induced epigenetic alterations

The role of tazemetostat in relapsed/refractory follicular lymphoma

Targeting EZH2 for the treatment of soft tissue sarcomas

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