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| Status |
Public on Sep 25, 2023 |
| Title |
PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Checkpoint inhibition (CPI), particularly that targeting the inhibitory co-receptor, programmed cell death protein (PD-1), has transformed cancer care. Although CPI can de repress cancer 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 immunological significance of PD-1 expression by tissue associated human Vδ1+ cells remains uncharacterised. Here we demonstrate that a transcriptional signature of intratumoral Vδ1+ cells predicts response to anti-PD-1 in patients with melanomas of relatively low neoantigen load. Moreover, by employing a protocol yielding substantial numbers of human skin γδ cells, we show that PD-1+ Vδ1+ cells display a transcriptomic programme of tissue-residence, survival/self-renewal, and functional competence distinct from the canonical exhaustion programme of co-located PD- 1+ CD8+ αβ T cells. Indeed, skin PD-1+ Vδ1+ cells retained effector responses to T cell receptor signalling that were inhibitable by PD-1 engagement and partially derepressed by CPI. The biological and therapeutic implications are both discussed.
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| Overall design |
In the study presented here, 785 human genes were profiled using NanoString's nCounter Immune Exhaustion Panel in FACS sorted PD1+ CD8 T cells (n=6 biological replicates/group), PD1- CD8 T cells (n=9 biological replicates/group), Vd1+ PD1+ gamma delta T cells (n=8 biological replicates/group) and Vd1+ PD1- gamma delta T cells (n=8 biological replicates/group) obtained from human skin samples cultured for a total of 6 weeks in human IL-2 and IL-15 (3 weeks 'on grid' isolation phase and 3 weeks 'off grid' expansion phase. See growth protocol described in line 77 for details).
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| Web link |
https://www.nature.com/articles/s43018-023-00690-0
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| Contributor(s) |
Davies D, Kamdar S, Woolf R, Zlatareva I, Iannitto ML, Morton C, Haque Y, Martin H, O'Neill O, Nussbaumer O, Hayday A, Wu Y |
| Citation(s) |
38172341 |
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| Submission date |
May 15, 2023 |
| Last update date |
Jan 17, 2024 |
| Contact name |
Shraddha Kamdar |
| E-mail(s) |
shraddha.kamdar@kcl.ac.uk
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| Organization name |
King’s College London
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| Department |
Peter Gorer Department of Immunobiology
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| Lab |
Immunosurveillance Lab
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| Street address |
Guys Hospital,Great Maze Pond, London Bridge
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| City |
London |
| ZIP/Postal code |
SE1 9RT |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL33412 |
Nanostring nCounter Immune Exhaustion Panel [NS_Hs_Exhaustion_v1.0] |
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| Samples (31)
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| Relations |
| BioProject |
PRJNA972675 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE232529_RAW.tar |
300.0 Kb |
(http)(custom) |
TAR (of RCC) |
| GSE232529_scaled_and_normalized_intensities.txt.gz |
56.4 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
| Processed data are available on Series record |
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