Related Experiment Video

Updated: Jun 25, 2025

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
09:15

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine

Published on: February 24, 2023

3.4K

Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell (cDC1) activation

Fenglian He1, Zhongen Wu1, Chenglong Liu1

  • 1Department of Pharmacology, Minhang Hospital, and Key Laboratory of Smart Drug Delivery, Shanghai Engineering Research Center of Immune Therapy, School of Pharmacy, Fudan University, Shanghai, 201203, China.

Signal Transduction and Targeted Therapy
|May 29, 2024
PubMed

Insights

Targeting B-cell lymphoma 9 and B-cell lymphoma 9-like (BCL9/BCL9L) enhances antigen presentation by conventional type 1 dendritic cells (cDC1). This boosts CD8+ T cell responses and delays tumor growth, offering a new cancer immunotherapy strategy.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Biology

Background:

  • Conventional type 1 dendritic cells (cDC1) are crucial for anti-tumor immunity.
  • B-cell lymphoma 9 and B-cell lymphoma 9-like (BCL9/BCL9L) are implicated in tumor growth and immune response modulation.
  • The precise role of oncogenic BCL9/BCL9L in impairing tumor antigen presentation remains unclear.

Purpose of the Study:

  • To investigate the impact of targeting BCL9/BCL9L on antigen presentation by cDC1 within the tumor microenvironment.
  • To elucidate the mechanisms by which BCL9/BCL9L affects cDC1 function and anti-tumor immunity.
  • To evaluate the therapeutic potential of BCL9/BCL9L inhibition in enhancing cancer immunotherapy.

Main Methods:

  • Pharmacological inhibition of BCL9/BCL9L using hsBCL9z96.
  • Utilizing Bcl9/Bcl9l knockout mouse models.
  • Employing single-cell transcriptomics analysis.
  • Investigating the XCL1-XCR1 axis and NF-κB/IRF1 signaling pathways.

Main Results:

  • Targeting BCL9/BCL9L significantly delayed tumor growth and promoted CD8+ T cell responses.
  • Inhibition of BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration.
  • The XCL1-XCR1 axis was identified as a key mediator of increased cDC1 activation and tumor infiltration.
  • Bcl9/Bcl9l deficient cDC1 exhibited superior activation and antigen presentation capabilities compared to WT cDC1, mediated by NF-κB/IRF1 signaling.

Conclusions:

  • Targeting BCL9/BCL9L is critical for cDC1-mediated antigen presentation of tumor antigens.
  • BCL9/BCL9L inhibition enhances CD8+ T cell activation and tumor infiltration, orchestrating a positive feedback loop for anti-tumor immunity.
  • Regulating cDC1 function via BCL9/BCL9L targeting represents a promising strategy to overcome immune suppression and improve cancer immunotherapy outcomes.

More Related Videos

Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy08:40

Preparation of Tumor Antigen-loaded Mature Dendritic Cells for Immunotherapy

Published on: August 1, 2013

18.3K
Chemical Conjugation of a Purified DEC-205-Directed Antibody with Full-Length Protein for Targeting Mouse Dendritic Cells In Vitro and In Vivo10:35

Chemical Conjugation of a Purified DEC-205-Directed Antibody with Full-Length Protein for Targeting Mouse Dendritic Cells In Vitro and In Vivo

Published on: February 5, 2021

3.4K

Related Concept Videos

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.
514
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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...
706
B Cell Activation and Differentiation01:24

B Cell Activation and Differentiation

The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
When naive B cells encounter a specific antigen that can bind to the B cell receptor (BCR) on their surface, they undergo sensitization to respond to the antigen's presence. Sensitization begins with...
1.7K
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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...
891
Antigen Presenting Cells01:22

Antigen Presenting Cells

The immune system is a complex network of cells and molecules that protects the body from foreign invaders. T cells, a type of white blood cell, play a crucial role in this process. They recognize and attack foreign substances, such as pathogens, that enter the body.
T cells require the help of antigen-presenting cells (APCs), which process foreign antigens into smaller fragments that can be recognized by T cells. These APCs are highly specialized cells that efficiently internalize antigens...
1.8K