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FAS signalling pathway is crucial for CAR T cell persistence

Nature Reviews Immunology volume 24, page 380 (2024)Cite this article

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Chimeric antigen receptor (CAR) T cell therapies have revolutionized the treatment of B cell and other malignancies, but the limited persistence of CAR T cells in vivo has restricted their clinical efficacy. The FAS–FASL receptor–ligand signalling pathway, which has a crucial role in regulating apoptosis, has been implicated in determining the persistence of CAR T cells. In a recent preprint (not peer reviewed), Yi et al. explore this relationship.

First, the authors used single-cell transcriptomics to evaluate immune and non-immune cells from healthy donors and individuals with diverse cancer types. They found that whereas FAS is expressed by fibroblasts, dendritic cells, regulatory T cells, as well as proliferating and exhausted T cells, the expression of FASLG (which encodes FASL) is restricted to T cells and natural killer (NK) cells. Moreover, using RNA in situ hybridization, the authors observed that CAR T cells had higher FASLG expression than endogenous T cells.

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  1. Preprint Club, Department of Immunology, University of Toronto, Toronto, Ontario, Canada

    Robyn Loves & Eyal Grunebaum

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  1. Robyn Loves
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  2. Eyal Grunebaum
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Correspondence to Robyn Loves.

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Loves, R., Grunebaum, E. FAS signalling pathway is crucial for CAR T cell persistence. Nat Rev Immunol 24, 380 (2024). https://doi.org/10.1038/s41577-024-01038-0

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  • DOI: https://doi.org/10.1038/s41577-024-01038-0

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