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DNA Tension Probes to Map the Transient Piconewton Receptor Forces by Immune Cells

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Taming Variability in T-Cell Mechanosensing.

Paula J Schultheiss¹, Aarya Pulkundwar¹, Wangqi Li²

¹Department of Biomedical Engineering, Columbia University, New York, NY 10027, USA.

|February 12, 2025

Summary

This summary is machine-generated.

Understanding variability in T-cell expansion is key for immunotherapy. This study found that effector T cells (T_Effs) drive mechanosensitive expansion, improving the reliability of these "living drugs".

Keywords:

CAR T-cell therapies biomaterials immunotherapy mechanosensing

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Area of Science:

Immunology
Biotechnology
Biomaterials Science

Background:

T-cell expansion is crucial for immunotherapy, often using stiff materials for activation.
Softer materials can enhance T-cell expansion, but individual variability hinders clinical application.
Mechanosensitive responses in T cells vary significantly between donors.

Purpose of the Study:

To identify the sources of variability in T-cell expansion.
To improve the reliability and success of T-cell expansion for immunotherapy.
To correlate T-cell mechanosensing with donor characteristics and cell phenotypes.

Main Methods:

Phenotypic characterization of T cells from healthy donors.
In vitro activation and expansion on soft and hard substrates.
Quantification of mechanosensing responses and correlation with demographic/phenotypic data.

Main Results:

Mechanosensitive T-cell expansion correlates with the percentage of effector T cells (T_Effs) in the initial population.
T_Effs mediate mechanosensitive expansion but are not the primary drivers of large-scale cell production.
Population-level expansion arises from complex interactions between different T-cell subtypes.

Conclusions:

Donor variability in T-cell expansion is linked to T_Eff cell populations and their interactions.
A framework for understanding and addressing T-cell variability is established.
This research enhances the reliability of T-cell expansion for clinical immunotherapy applications.