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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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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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PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

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The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
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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.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
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The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

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The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
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Related Experiment Video

Updated: Sep 18, 2025

Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells
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Measuring Mitochondrial Function of Naïve and Effector CD8 T Cells

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T cell exhaustion: Focus on molecular pathways.

Qiucai Dang1

  • 1Zhumadian Preschool Education College, Zhumadian, Henan province 463000, China.

Pathology, Research and Practice
|June 24, 2025
PubMed
Summary

T cell exhaustion impairs anti-cancer immunity but can be reversed. Understanding molecular pathways and metabolic dysfunction in exhausted T cells is key to developing new therapies for cancer treatment.

Area of Science:

  • Immunology
  • Cancer Biology
  • Metabolic Dysfunction

Background:

  • T cell exhaustion is a state of T cell dysfunction that arises during chronic infections and cancer.
  • While initially a protective mechanism against excessive immune damage, T cell exhaustion can hinder the immune system's ability to fight cancer.
  • The status of T cells within tumors is a critical factor influencing the success of immune checkpoint blockade therapies.

Purpose of the Study:

  • To review the molecular pathways driving T cell exhaustion.
  • To explore the role of metabolic dysfunction, microRNA regulation, and cytokine environment in T cell exhaustion.
  • To discuss potential therapeutic strategies to overcome T cell exhaustion in cancer.

Main Methods:

  • Review of molecular pathways.
Keywords:
Immune checkpoint blockadeMalignanciesNR4AT cell exhaustion

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Real-time Monitoring of Mitochondrial Respiration in Cytokine-differentiated Human Primary T Cells
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  • Analysis of transcription factor activity (Nr4a1, Nr4a2, Nr4a3).
  • Examination of metabolic profiles and mitochondrial function in exhausted T cells.

    • Main Results:

    • T cell exhaustion is characterized by increased transcription of Nr4a genes and immune checkpoint molecules.
    • Exhausted T cells exhibit altered metabolism, including impaired glucose metabolism and mitochondrial dysfunction.
    • This metabolic dysfunction leads to reduced proliferation and cytotoxic capacity against cancer cells.

    Conclusions:

    • T cell exhaustion presents a significant barrier to effective anti-tumor immunity.
    • Targeting molecular pathways and metabolic dysfunctions offers promising therapeutic avenues.
    • Revitalizing exhausted T cells could enhance the efficacy of cancer immunotherapies.