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Redefining PD1 as a guardian of stem-like T cells

Nature Reviews Immunology volume 25, page 3 (2025)Cite this article

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In the face of tumour and viral challenges, TCF1+PD1+ stem-like T cells (TSL cells) are a crucial CD8+ T cell subset capable of self-renewal and of replenishing cytotoxic effector T cells. Crucially, TSL cell populations expand upon immune checkpoint blockade, thus potentiating the therapeutic recovery of antitumour T cell responses. In a recent preprint (not peer reviewed), Hor et al. interrogate TSL cell niches in tumour-draining lymph nodes (tDLNs). They define a SLAMF6+ TSL cell subset with high T cell receptor (TCR) affinity, maintenance of which is regulated by PD1 signalling and prolonged association with conventional type 1 dendritic cells (cDC1s).

The authors used 3D multiplex immunofluorescence imaging in optically cleared tDLNs of mice bearing subcutaneous KP-OVA tumours, enabling the spatial and functional profiling of tumour-targeting CD8+ T cells. An XCR1 fluorescent reporter mouse model enabled the additional visualization of XCR1+ cDC1s.

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  1. Preprint Club, University of Oxford, Oxford, UK

    Matthew Jackson & Eileen E. Parkes

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  1. Matthew Jackson
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  2. Eileen E. Parkes
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Correspondence to Matthew Jackson.

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Jackson, M., Parkes, E.E. Redefining PD1 as a guardian of stem-like T cells. Nat Rev Immunol 25, 3 (2025). https://doi.org/10.1038/s41577-024-01117-2

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  • DOI: https://doi.org/10.1038/s41577-024-01117-2

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