Related Experiment Video

Updated: Oct 2, 2025

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells
09:04

Analysis of Human T Cell Activity in an Allogeneic Co-Culture Setting of Pre-Treated Tumor Cells

Published on: March 7, 2025

754

EZH2, a prominent orchestrator of genetic and epigenetic regulation of solid tumor microenvironment and immunotherapy

Shanshan Sun1, Feng Yu2, Danying Xu3

  • 1Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China; Cancer Institute, Zhejiang University, Hangzhou, Zhejiang 310058, China; Department of Medicine, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America; Department of Surgery, the University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States of America.

Biochimica Et Biophysica Acta. Reviews on Cancer
|February 26, 2022
PubMed

Insights

Enhancer of Zeste Homolog 2 (EZH2) drives cancer immune suppression by altering tumor microenvironment (TME) cells. Targeting EZH2 may enhance immune checkpoint blockade (ICB) therapy effectiveness for improved patient survival.

Area of Science:

  • Oncology
  • Immunology
  • Epigenetics

Background:

  • Immune checkpoint blockade (ICB) shows promise in cancer therapy.
  • Enhancer of Zeste Homolog 2 (EZH2), a histone methyltransferase, is linked to solid tumor development.
  • The role of EZH2 in cancer immune resistance is not fully understood.

Purpose of the Study:

  • To review the multifaceted roles of EZH2 in modulating the tumor microenvironment (TME).
  • To explore EZH2's impact on various immune and stromal cells within the TME.
  • To discuss the potential of EZH2 inhibitors in overcoming cancer immunotherapy resistance.

Main Methods:

  • Literature review of EZH2 functions in cancer and immunology.
  • Analysis of EZH2's epigenetic and transcriptomic effects on TME components.
  • Compilation of ongoing clinical trials involving EZH2 inhibitors.

Main Results:

  • EZH2 regulates both innate and adaptive immunity within the TME.
  • EZH2 induces epigenetic and transcriptomic changes that promote an immunosuppressive TME.
  • EZH2 influences tumor cells, T cells, macrophages, NK cells, MDSCs, DCs, fibroblasts, and MSCs.

Conclusions:

  • EZH2 plays a critical role in establishing an immune-suppressive tumor microenvironment.
  • Targeting EZH2 offers a potential strategy to enhance the efficacy of immune checkpoint blockade.
  • Combinational therapy involving EZH2 inhibitors may improve survival outcomes for cancer patients.
Keywords:
Enhancer of Zeste Homolog 2EpigeneticsImmunotherapySolid tumorTumor microenvironment

More Related Videos

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells10:26

In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells

Published on: January 20, 2019

12.5K
Predictive Immune Modeling of Solid Tumors08:50

Predictive Immune Modeling of Solid Tumors

Published on: February 25, 2020

7.1K

Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.8K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
708
Epigenetic Regulation01:37

Epigenetic Regulation

Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
X-chromosome...
3.2K
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
7.0K
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal01:22

Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal

Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.3K
Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.8K