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T Cell Activation and Clonal Selection

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Related Experiment Video

Updated: Oct 2, 2025

Dynamic Imaging of Chimeric Antigen Receptor T Cells with [18F]Tetrafluoroborate Positron Emission Tomography/Computed Tomography

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Published on: February 17, 2022

Knowns and Unknowns about CAR-T Cell Dysfunction.

Aleksei Titov^1,2, Yaroslav Kaminskiy², Irina Ganeeva¹

¹Institute of Fundamental Medicine and Biology, Kazan Federal University, 420008 Kazan, Russia.

|February 25, 2022

Summary

This summary is machine-generated.

Chimeric antigen receptor (CAR) T cell therapy shows promise for cancer, but T cell dysfunction, including exhaustion and senescence, hinders its effectiveness. Strategies to overcome this dysfunction are crucial for improving CAR-T cell efficacy.

Keywords:

CAR tonic signaling CAR-T cell T cell dysfunction T cell exhaustion T cell senescence chimeric antigen receptor

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Published on: July 25, 2025

Area of Science:

Immunology
Cancer Biology
Cellular Therapy

Background:

Chimeric antigen receptor (CAR) T cell immunotherapy is a potent cancer treatment strategy.
T cells and CAR-T cells often become dysfunctional in the tumor microenvironment, limiting their antitumor activity.
Cancer cells exploit intrinsic T cell defense mechanisms, leading to dysfunction such as exhaustion and senescence.

Purpose of the Study:

To provide an overview of T cell dysfunctional states, specifically exhaustion and senescence.
To examine the impact of T cell dysfunction on CAR-T cell therapeutic potential.
To discuss current strategies for mitigating CAR-T cell exhaustion.

Main Methods:

Review of existing literature on T cell dysfunction in cancer.
Analysis of mechanisms underlying T cell exhaustion and senescence.
Exploration of epigenetic and transcriptional modulation for CAR-T cell enhancement.

Main Results:

T cell exhaustion impairs proliferation and cytokine secretion, often identified by inhibitory receptor expression.
T cell senescence involves permanent cell cycle arrest while retaining cytotoxicity.
T cell dysfunction significantly impacts the efficacy of CAR-T cell therapy.

Conclusions:

Understanding T cell dysfunction is critical for advancing CAR-T cell therapy.
Mitigation strategies, particularly those targeting epigenetic and transcriptional regulation, offer potential to enhance CAR-T cell function.
Further research into overcoming T cell exhaustion and senescence is essential for maximizing immunotherapy outcomes.