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Related Concept Videos

Master Transcription Regulators02:23

Master Transcription Regulators

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Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a  complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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Regulation of Hematopoietic Stem Cells01:01

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Lineage Commitment01:21

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Commitment is the  process whereby stem cells:
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Somatic to iPS Cell Reprogramming01:29

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Reprogramming alters the gene expression in somatic cells, transforming them into induced pluripotent stem (iPS) cells over several generations. Scientists can reprogram cells by introducing genes for four transcription factors—Oct4, Sox2, Klf4, and c-Myc (OSKM) by viral or non-viral methods. These factors are also known as Yamanaka factors after Shinya Yamanaka, who first generated iPS cells using mouse skin cells. Yamanaka was awarded the Nobel Prize in Physiology or Medicine in 2012...
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T Cell Activation and Clonal Selection01:22

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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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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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FOXO1 is a master regulator of CAR T memory programming.

Alexander Doan1, Katherine P Mueller2,3,4,5,6, Andy Chen7,8,9

  • 1Center for Cancer Cell Therapy, Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.

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Summary

The transcription factor FOXO1 promotes memory programs and prevents exhaustion in CAR T cells, enhancing their persistence and anti-tumor activity. This discovery offers a new strategy for improving CAR T cell therapies.

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Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • CAR T cell therapy persistence is limited, hindering treatment for B cell malignancies and solid tumors.
  • Memory gene expression, like TCF7 (TCF1), is crucial for CAR T cell response and long-term persistence.
  • Understanding the regulators of CAR T cell memory and exhaustion is critical for enhancing therapeutic efficacy.

Conclusions:

  • FOXO1 acts as a key pioneer transcription factor that promotes memory programs and restrains exhaustion in human CAR T cells.
  • FOXO1-mediated memory reprogramming can significantly enhance the persistence and potency of CAR T cells for cancer immunotherapy.
  • Targeting pioneer factors like FOXO1 represents a promising strategy for optimizing therapeutic T cell states and improving clinical outcomes.