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Related Concept Videos

Tumor Immunotherapy01:27

Tumor Immunotherapy

398
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 Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

531
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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T Cell Types and Functions01:24

T Cell Types and Functions

617
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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Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

725
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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The Tumor Microenvironment02:17

The Tumor Microenvironment

6.4K
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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The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

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Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
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Related Experiment Video

Updated: May 10, 2025

Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
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CTLA-4-two pathways to anti-tumour immunity?

Frank J Ward1, Paul T Kennedy2, Farah Al-Fatyan1

  • 1Medical Sciences and Nutrition, Institute of Medical Sciences, School of Medicine, University of Aberdeen, Aberdeen, United Kingdom.

Immunotherapy Advances
|April 23, 2025
PubMed
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Immune checkpoint inhibitors (ICIs) advance cancer therapy by targeting inhibitory receptors. Understanding CTLA-4

Keywords:
CTLA-4immune checkpoint inhibitorregulatory T cells (Treg)soluble CTLA-4 (sCTLA-4)

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Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
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Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
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Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens
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Area of Science:

  • Immunology and Cancer Therapy
  • Tumor Microenvironment (TME) Research

Background:

  • Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enhancing anti-tumor immunity via targets like CTLA-4, PD-1, PD-L1, and LAG-3.
  • Patient response and tolerance to ICIs vary, necessitating biomarkers for outcome prediction and a deeper understanding of ICI interactions within the tumor microenvironment (TME).
  • Anti-CTLA-4 antibodies, while early ICI entrants, have shown less efficacy than PD-1/PDL-1 axis inhibitors due to complex mechanisms of action.

Purpose of the Study:

  • To elucidate the dual mechanisms of anti-CTLA-4 antibody efficacy: direct T-cell enhancement versus regulatory T-cell (TREG) elimination.
  • To investigate the role of soluble CTLA-4 (sCTLA-4) as both a potential confounder and a therapeutic agent in cancer immunotherapy.

Main Methods:

  • Review and examination of existing evidence on CTLA-4 blockade mechanisms.
  • Analysis of the dual roles of regulatory T cells (TREGs) in anti-CTLA-4 therapy response.
  • Exploration of soluble CTLA-4 (sCTLA-4) implications in cancer immunity.

Main Results:

  • Evidence supports two distinct pathways for anti-CTLA-4 efficacy: direct T-cell activation and TREG suppression.
  • These mechanisms exhibit differing antagonistic characteristics, contributing to variable therapeutic outcomes.
  • Soluble CTLA-4 (sCTLA-4) presents a complex factor, potentially impacting current ICI therapies while offering novel therapeutic possibilities.

Conclusions:

  • The dual mechanisms of CTLA-4 blockade require further investigation to optimize anti-CTLA-4 therapies.
  • Understanding the interplay between CTLA-4, TREGs, and the TME is crucial for improving cancer treatment efficacy.
  • Soluble CTLA-4 (sCTLA-4) warrants further study as a biomarker and a potential therapeutic strategy for antigen-specific anti-tumor immunity.