The Heightened Importance of EZH2 in Cancer Immunotherapy

Abstract

The transcriptional inhibitor histone methyltransferase enhancer of zeste homolog 2 (EZH2) predominantly targets genes involved in tumor suppression. EZH2 is highly expressed in a variety of human malignancies and promotes carcinogenesis and malignant transformation. Recent research has indicated that altering the tumor microenvironment by focusing on epigenetic variables can improve antitumor immunity. Recent research has also revealed that EZH2 has pleiotropic functions in immune and malignant cells. EZH2 inhibition could be a promising strategy to improve the outcomes of current immunotherapies. Based on the role of EZH2 in the immunomodulation of both immune and tumor cells, we evaluated the effect of EZH2 on tumor immunity in this review. We also highlight improvements in combined EZH2-targeted treatment and immunotherapy.

EZH2 Expression in Head-and-Neck Squamous Cell Cancer in Young Patients

“…It is involved in regulating cellular survival (via enhancing both proliferation and hypoxia-tolerance), the immunogenicity of tumor cells (through the down-regulation of MHC Class I antigen presentation, hence the immunological visibility [9]), and the capacity for metastasis formation (through modulating interactions with the extracellular matrix) [10][11][12][13][14][15][16][17]. EZH2 exerts its functions both as an enzimatic catalytic subunit of polycomb repressive complex 2 (PRC2), chiefly through regulating genome structure and gene expression through the trimethylation of Lys-27 in histone 3 (H3K27me3), and also PRC2-independently by modulating further mediators, including the hypoxia-inducible factor-1α (HIF-1α) and FoxM1 [10][11][12][13][14][15][16][17]. Although reviewing all known functions of EZH2 would far exceed the scope of this work, we summarized its main functions associated with tumor cell viability and survival, as shown in Figure 1.…”

“…The PRC2-linked effects of EZH2 also support cellular proliferation and might hinder differentiation. The tumor suppressor TP53 acts against the expression of PRC2 members (EED and EZH2) [10][11][12][13][14][15][16][17].…”