Related Experiment Video
Updated: Mar 29, 2026
07:36
Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
7.9K
Targeting Mettl8-Tcf1 axis promotes CD8+ TPEX differentiation and antitumor immunity.
Jiaxi Song1, Dan Cui2, Jiabao Wang1
1State Key Laboratory of Immune Response and Immunotherapy, School of Basic Medical Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China , Hefei, China.
The Journal of Experimental Medicine
|March 27, 2026
Summary
Mettl8 regulates T cell exhaustion in cancer immunotherapy. Inhibiting Mettl8 promotes effective T cell differentiation and enhances anti-PD-1 therapy, offering a new therapeutic strategy.
Area of Science:
- Immunology
- Cancer Biology
- Epigenetics
Background:
- CD8+ T cell exhaustion hinders cancer immunotherapy effectiveness.
- The epigenetic mechanisms governing T cell exhaustion subset differentiation remain largely unknown.
Purpose of the Study:
- To investigate the role of RNA methyltransferase Mettl8 in regulating T cell exhaustion.
- To explore Mettl8 as a potential therapeutic target for improving cancer immunotherapy.
Main Methods:
- Analysis of Mettl8 expression in T cell subsets from cancer patients and murine models.
- Investigating the mechanistic link between Mettl8, TCF7, and TCF1.
- Assessing the therapeutic potential of Mettl8 inhibition alone and in combination with anti-PD-1 therapy.
Main Results:
- Mettl8 expression is higher in progenitor exhausted T (TPEX) cells than terminally exhausted (TEX) cells and is downregulated in anti-PD-1 responding lung cancer patients.
- Mettl8 deletion in murine models enhances TPEX differentiation into intermediate exhausted T (Int-TEX) cells, restraining tumor growth.
- Mettl8 stabilizes TCF7 mRNA via m3C modification, enhances TCF1 protein, and maintains TPEX stemness by facilitating chromatin looping at the Tox locus.
Conclusions:
- Mettl8 is a critical regulator of TPEX cell fate and differentiation.
- Pharmacological inhibition of Mettl8 promotes T cell differentiation and tumor control, synergizing with anti-PD-1 therapy.
- Mettl8 represents a promising therapeutic target for overcoming T cell exhaustion in cancer immunotherapy.
Related Concept Videos
01:27Cytotoxic T Cells-mediated Immune Response
8.2K
Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
8.2K
01:22T Cell Activation and Clonal Selection
17.3K
T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
Naive T cells that have not yet encountered an antigen express two primary CD...
17.3K
01:27Tumor Immunotherapy
2.2K
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.
2.2K
01:24T Cell Types and Functions
3.2K
When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
3.2K