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Related Concept Videos

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.
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The Tumor Microenvironment02:17

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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...
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Tumor Immunotherapy

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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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Abnormal Proliferation02:23

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Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
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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...
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Related Experiment Video

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In Vitro Differentiation of Human CD4+FOXP3+ Induced Regulatory T Cells (iTregs) from Naïve CD4+ T Cells Using a TGF-β-containing Protocol
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IL-23 stabilizes an effector Treg cell program in the tumor microenvironment.

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Interleukin-23 (IL-23) fuels tumor growth by activating regulatory T cells (Tregs). Targeting the IL-23/IL-23R pathway may enhance antitumor immunity.

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Area of Science:

  • Immunology
  • Oncology

Background:

  • Interleukin-23 (IL-23) is a pro-inflammatory cytokine linked to tumor progression.
  • The precise mechanisms by which IL-23 promotes tumor growth remain incompletely understood.

Purpose of the Study:

  • To elucidate the cellular sources and targets of IL-23 in the tumor microenvironment.
  • To investigate the role of IL-23 in regulating regulatory T cell (Treg) function and tumor promotion.

Main Methods:

  • Analysis of IL-23 production in tumor-associated macrophages (TAMs) from mouse and human tumors.
  • Identification and characterization of IL-23-sensing regulatory T cells (Tregs) within the tumor microenvironment.
  • Genetic ablation of the IL-23 receptor (Il23r) in Tregs in preclinical cancer models.

Main Results:

  • Tumor-associated macrophages (TAMs) were identified as the primary source of IL-23.
  • A subset of tumor-infiltrating Tregs was found to sense IL-23 and exhibit a suppressive phenotype.
  • Genetic deletion of Il23r in Tregs abrogated the tumor-promoting effects of IL-23.
  • IL-23 signaling was shown to be critical for the maintenance and stabilization of effector Tregs via Foxp3.

Conclusions:

  • IL-23 promotes tumor growth primarily by enhancing the suppressive function of tumor-infiltrating Tregs.
  • Targeting the IL-23/IL-23R axis presents a potential therapeutic strategy to stimulate antitumor immunity.