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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

1.7K
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.
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T Cell Types and Functions01:24

T Cell Types and Functions

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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...
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Radiotherapy induces YTHDF2 in dendritic cells impairing cross-presentation and T cell function.

Dapeng Chen1,2, Liangliang Wang3, Chuangyu Wen1,2

  • 1Department of Radiation and Cellular Oncology, University of Chicago, Chicago, IL, USA.

The Journal of Experimental Medicine
|November 6, 2025
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Summary
This summary is machine-generated.

Radiotherapy failure and metastasis are linked to radiation-induced immune suppression in dendritic cells (DCs). Targeting YTHDF2 in DCs overcomes this, enhancing cancer treatment and vaccines.

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Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Metastatic progression is a primary reason for radiotherapy failure.
  • Mechanisms linking radiotherapy to immune suppression and metastasis are not well understood.

Purpose of the Study:

  • To identify radiation-induced immune checkpoints in dendritic cells (DCs).
  • To investigate the role of YTHDF2 in radiotherapy resistance and metastasis.
  • To explore YTHDF2 targeting as a therapeutic strategy.

Main Methods:

  • Analysis of patient biopsies from a clinical trial (NCT03223155).
  • Investigated the molecular mechanisms of YTHDF2 regulation by ionizing radiation.
  • Assessed the impact of YTHDF2 on T cell activation and tumor control in preclinical models.

Main Results:

  • Increased YTHDF2 expression in DCs post-radiotherapy correlates with treatment failure.
  • Ionizing radiation induces SPI1, which upregulates YTHDF2 in DCs.
  • YTHDF2 promotes degradation of Notch pathway regulators, impairing T cell activation and promoting immune evasion.
  • Targeting YTHDF2 restored DC immunogenicity and enhanced radiotherapy efficacy.

Conclusions:

  • YTHDF2 acts as a radiation-induced immune checkpoint in DCs.
  • Targeting YTHDF2 is a promising strategy to overcome radiotherapy resistance and metastasis.
  • Combination therapy with YTHDF2 inhibition and radiotherapy may improve cancer treatment outcomes and DC-based vaccines.