PD-1 defines a distinct, functional, tissue-adapted state in Vδ1 + T cells with implications for cancer immunotherapy.

Autor: Davies D; Peter Gorer Department of Immunobiology, King's College London, London, UK.; Centre for Inflammation Biology and Cancer Immunology, King's College London, London, UK., Kamdar S; Peter Gorer Department of Immunobiology, King's College London, London, UK.; Centre for Inflammation Biology and Cancer Immunology, King's College London, London, UK., Woolf R; Peter Gorer Department of Immunobiology, King's College London, London, UK.; St. John's Institute of Dermatology, Guy's Hospital, London, UK., Zlatareva I; Peter Gorer Department of Immunobiology, King's College London, London, UK., Iannitto ML; Peter Gorer Department of Immunobiology, King's College London, London, UK., Morton C; Peter Gorer Department of Immunobiology, King's College London, London, UK.; Department of Medical Oncology, Guy's Hospital, London, UK., Haque Y; Peter Gorer Department of Immunobiology, King's College London, London, UK., Martin H; Immunosurveillance Laboratory, Francis Crick Institute, London, UK., Biswas D; Academic Foundation Programme, King's College Hospital, London, UK., Ndagire S; King's Health Partners Cancer Biobank, Guy's Hospital, London, UK., Munonyara M; Department of Cellular Pathology, St. Thomas' Hospital, London, UK., Gillett C; King's Health Partners Cancer Biobank, Guy's Hospital, London, UK., O'Neill O; Advanced Sequencing Facility, Francis Crick Institute, London, UK., Nussbaumer O; Peter Gorer Department of Immunobiology, King's College London, London, UK., Hayday A; Peter Gorer Department of Immunobiology, King's College London, London, UK. adrian.hayday@kcl.ac.uk.; Centre for Inflammation Biology and Cancer Immunology, King's College London, London, UK. adrian.hayday@kcl.ac.uk.; Immunosurveillance Laboratory, Francis Crick Institute, London, UK. adrian.hayday@kcl.ac.uk., Wu Y; Peter Gorer Department of Immunobiology, King's College London, London, UK. yin.wu@kcl.ac.uk.; Centre for Inflammation Biology and Cancer Immunology, King's College London, London, UK. yin.wu@kcl.ac.uk.; Department of Medical Oncology, Guy's Hospital, London, UK. yin.wu@kcl.ac.uk.
Jazyk: angličtina
Zdroj: Nature cancer [Nat Cancer] 2024 Mar; Vol. 5 (3), pp. 420-432. Date of Electronic Publication: 2024 Jan 03.
DOI: 10.1038/s43018-023-00690-0
Abstrakt: Checkpoint inhibition (CPI), particularly that targeting the inhibitory coreceptor programmed cell death protein 1 (PD-1), has transformed oncology. Although CPI can derepress cancer (neo)antigen-specific αβ T cells that ordinarily show PD-1-dependent exhaustion, it can also be efficacious against cancers evading αβ T cell recognition. In such settings, γδ T cells have been implicated, but the functional relevance of PD-1 expression by these cells is unclear. Here we demonstrate that intratumoral TRDV1 transcripts (encoding the TCRδ chain of Vδ1 + γδ T cells) predict anti-PD-1 CPI response in patients with melanoma, particularly those harboring below average neoantigens. Moreover, using a protocol yielding substantial numbers of tissue-derived Vδ1 + cells, we show that PD-1 + Vδ1 + cells display a transcriptomic program similar to, but distinct from, the canonical exhaustion program of colocated PD-1 + CD8 + αβ T cells. In particular, PD-1 + Vδ1 + cells retained effector responses to TCR signaling that were inhibitable by PD-1 engagement and derepressed by CPI.
(© 2024. The Author(s).)
Databáze: MEDLINE
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