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Related Concept Videos

Tumor Immunotherapy01:27

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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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

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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...
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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.
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Cell-mediated Immune Responses01:40

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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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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...
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Related Experiment Video

Updated: May 22, 2025

Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
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Activated T Cells Break Tumor Immunosuppression by Macrophage Reeducation.

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T-cell activation suppresses hematopoietic prostaglandin-D2 synthase (HPGDS) in tumor macrophages, which normally promote cancer growth. Targeting HPGDS enhances anti-tumor immunity and improves immunotherapy response.

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Area of Science:

  • Immunology
  • Oncology
  • Cancer Research

Background:

  • Tumor-associated macrophages (TAMs) often exhibit pro-tumoral functions.
  • The role of prostaglandin D2 (PGD2) in the tumor microenvironment is complex.
  • T-cell activation is crucial for anti-tumor immunity but can be suppressed within the tumor microenvironment.

Purpose of the Study:

  • To elucidate the mechanism by which T-cell activation influences TAM function in melanoma.
  • To investigate the role of hematopoietic prostaglandin-D2 synthase (HPGDS) in mediating TAM pro-tumoral phenotypes.
  • To explore HPGDS as a therapeutic target for overcoming immunotherapy resistance.

Main Methods:

  • Analysis of HPGDS transcription in tumor-associated macrophages (TAMs) from human and murine melanomas.
  • Investigation of TNFα signaling pathways in regulating HPGDS.
  • Assessment of Prostaglandin-D2 (PGD2) autocrine loops in TAMs via DP1 and DP2 receptors.
  • Evaluation of genetic and pharmacologic HPGDS inhibition on TAM phenotype and CD8+ T-cell activity.
  • Correlation of HPGDS expression levels with response to αPD1 immunotherapy in patients and mice.

Main Results:

  • T-cell activation in melanoma suppresses HPGDS transcription in TAMs via TNFα signaling.
  • HPGDS establishes a PGD2 autocrine loop in TAMs, sustaining their pro-tumoral state and inhibiting CD8+ T cells.
  • Targeting HPGDS promotes anti-tumoral TAM features, enhances CD8+ T-cell recruitment and function, and sensitizes tumors to αPD1.
  • HPGDS overexpression or TNFα blockade leads to immunotherapy resistance by maintaining a pro-tumoral TAM phenotype.

Conclusions:

  • T-cell activation regulates the innate immune system by modulating TAM function through HPGDS.
  • HPGDS/PGD2 signaling in TAMs is a key mechanism driving immunotherapy resistance.
  • Targeting HPGDS presents a promising strategy to overcome αPD1 resistance and enhance anti-tumor immunity.