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Related Concept Videos

T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

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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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Cell-mediated Immune Responses01:40

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T Cell Types and Functions01:24

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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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Cells of the Adaptive Immune Response01:23

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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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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

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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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Using Human Induced Pluripotent Stem Cells for the Generation of Tumor Antigen-specific T Cells
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Cellular networks controlling T cell persistence in adoptive cell therapy.

Jack D Chan1,2, Junyun Lai1,2, Clare Y Slaney1,2

  • 1Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

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Less differentiated T cells, including those with stem-like properties, offer superior anti-cancer effects due to better expansion and persistence. Strategies are emerging to enhance T cell therapy for solid tumors.

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Area of Science:

  • Immunology
  • Cancer Biology
  • Cell Therapy

Background:

  • T cell differentiation status critically impacts anti-tumor activity.
  • Less differentiated T cells exhibit enhanced expansion and long-term persistence, crucial for effective cancer immunotherapy.
  • Stem-like memory or precursor T cell phenotypes in cancer patients correlate with improved therapeutic outcomes.

Purpose of the Study:

  • To review current barriers and strategies for optimizing T cell expansion and persistence in adoptive T cell immunotherapy for solid cancers.
  • To highlight advances in generating more persistent and functional chimeric antigen receptor T cells.
  • To discuss the role of T cell differentiation in anti-tumor responses.

Main Methods:

  • Review of existing literature on T cell differentiation, function, and immunotherapy.
  • Analysis of epigenetic and transcriptional regulation of T cell states.
  • Examination of novel methods for T cell generation, including culture techniques and programming modulation.

Main Results:

  • Less differentiated T cells demonstrate superior anti-tumor effects compared to fully differentiated effector T cells.
  • Stem-like T cell phenotypes are associated with better therapeutic outcomes in cancer patients.
  • Novel strategies, including pre-infusion culture and programming modulation, enhance T cell persistence and resistance to dysfunction.

Conclusions:

  • Optimizing T cell differentiation status is key to improving adoptive T cell immunotherapy efficacy.
  • Advances in understanding T cell biology enable the development of more potent and persistent engineered T cells for cancer treatment.
  • Overcoming barriers to T cell expansion and persistence is essential for successful solid tumor immunotherapy.