Related Experiment Video
Updated: Jun 25, 2025
10:13
Tailoring In Vivo Cytotoxicity Assays to Study Immunodominance in Tumor-specific CD8+ T Cell Responses
Published on: May 6, 2019
9.0K
β-Catenin in Dendritic Cells Negatively Regulates CD8 T Cell Immune Responses through the Immune Checkpoint Molecule
Chunmei Fu1,2,3, Jie Wang1,2,3, Tianle Ma4
1Center for Cutaneous Biology and Immunology, Department of Dermatology, Henry Ford Health, Detroit, MI 48202, USA.
Vaccines
|May 25, 2024
Summary
Activating beta-catenin in dendritic cells upregulates Tim-3, inhibiting CD8 T cell immunity. Targeting this beta-catenin/Tim-3 axis with DC vaccines and anti-Tim-3 therapy enhances anti-tumor responses.
Area of Science:
- Immunology
- Cancer Biology
- Molecular Medicine
Background:
- Beta-catenin in dendritic cells (DCs) is crucial for T cell tolerance, but its precise mechanisms are unclear.
- Activation of beta-catenin in DCs has been linked to immune suppression, necessitating further investigation into its downstream effectors.
Purpose of the Study:
- To elucidate the role of beta-catenin in regulating CD8 T cell responses within DCs.
- To identify novel molecular targets for enhancing DC-based cancer immunotherapy.
Main Methods:
- Utilized a cDC1-targeted vaccine model (anti-DEC-205-hgp100) in CD11c-beta-catenin(active) mice.
- Performed single-cell RNA sequencing (scRNA-seq) to analyze gene expression changes in T cells.
- Administered anti-Tim-3 antibody treatment in conjunction with DC vaccination in tumor-bearing mice.
Main Results:
- Beta-catenin activation in cDC1s upregulates the inhibitory molecule Tim-3.
- Beta-catenin in DCs suppresses CD8 T cell effector function and proliferation via transcriptional regulation.
- Anti-Tim-3 antibody treatment restored CD8 T cell responses and improved anti-tumor efficacy when combined with DC vaccines.
Conclusions:
- The beta-catenin/Tim-3 axis represents a novel inhibitory mechanism for anti-tumor CD8 T cell immunity.
- Combination immunotherapy using DC-targeted vaccines and anti-Tim-3 antibodies shows promise for enhancing anti-cancer treatment efficacy.
Related Concept Videos
01:23Catenins
2.3K
Catenins are characterized by multiple binding domains and dynamic structures that allow them to function as linker proteins in cell junction complexes. All catenins, except α-catenin, contain a characteristic protein sequence called the armadillo repeat and are therefore also called armadillo proteins.
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
Catenins in Cell Junctions
Catenins bind to cell adhesion molecules such as cadherins and link them to different cytoskeletal proteins depending on the type of cell junction. At the...
2.3K
01:24T Cell Types and Functions
1.0K
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...
1.0K
02:54Canonical Wnt Signaling Pathway
8.7K
The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
8.7K
01:22T Cell Activation and Clonal Selection
706
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...
706
01:27Cytotoxic T Cells-mediated Immune Response
892
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...
892
01:16TGF - β Signaling Pathway
7.3K
The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors...
7.3K