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CAR T-cell behavior and function revealed by real-time imaging

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Abstract

Adoptive transfer of T-cells expressing chimeric antigen receptors (CAR) has shown remarkable clinical efficacy against advanced B-cell malignancies. Nonetheless, the field of CAR T-cells is currently facing several major challenges. In particular, the CAR T-cell strategy has not yet produced favorable clinical responses when targeting solid tumors. In this context, it is of paramount importance to understand the determinants that limit the efficacy of T-cell-based immunotherapy. Characterization of CAR T-cells is usually based on flow cytometry and whole-transcriptome profiling. These approaches have been very valuable to determine intrinsic elements that condition T-cell ability to proliferate and expand. However, they do not take into account spatial and kinetic aspects of T-cell responses. In particular, in order to control tumor growth, CAR T-cells need to enter into the tumor, migrate within a complex tumor environment, and form productive conjugates with their targets. Advanced imaging techniques combined with innovative preclinical models represent promising tools to uncover the dynamics of CAR T-cells. In this review, we will discuss recent results on the biology of engineered T-cells that have been obtained with real-time imaging microscopy. Important notions have emerged from these imaging-based studies, such as the multi-killing potential of CAR T-cells. Finally, we will highlight how imaging techniques combined with other tools can solve remaining unresolved questions in the field of engineered T-cells.

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Abbreviations

APC:

Antigen-presenting cell

CAR:

Chimeric antigen receptor

IFN:

Interferon

TIL:

Tumor-infiltrating lymphocytes

ICAM:

Intercellular adhesion molecule

pMHC:

Peptide-major histocompatibility

TCR:

T-cell receptor

TME:

Tumor microenvironment

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Funding

This research was funded by Ligue National Contre le Cancer, grant number EL2020.LNCC/EmD.

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Authors and Affiliations

  1. Université Paris Cité, CNRS, INSERM, Equipe Labellisée Ligue Contre le Cancer, Institut Cochin, INSERM U1016, 22 rue Méchain, F-75014, Paris, France

    David Espie & Emmanuel Donnadieu

  2. Invectys, Paris, France

    David Espie

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  1. David Espie
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  2. Emmanuel Donnadieu
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DE and ED conceived, wrote the article, and designed the figure.

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Correspondence to Emmanuel Donnadieu.

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Espie, D., Donnadieu, E. CAR T-cell behavior and function revealed by real-time imaging. Semin Immunopathol 45, 229–239 (2023). https://doi.org/10.1007/s00281-023-00983-7

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