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PD-1 defines a distinct, functional, tissue-adapted state in Vδ1+ T cells with implications for cancer immunotherapy.
Davies, Daniel; Kamdar, Shraddha; Woolf, Richard; Zlatareva, Iva; Iannitto, Maria Luisa; Morton, Cienne; Haque, Yasmin; Martin, Hannah; Biswas, Dhruva; Ndagire, Susan; Munonyara, Martina; Gillett, Cheryl; O'Neill, Olga; Nussbaumer, Oliver; Hayday, Adrian; Wu, Yin.
Afiliación
  • Davies D; Peter Gorer Department of Immunobiology, King's College London, London, UK.
  • Kamdar S; 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.
  • Zlatareva I; Centre for Inflammation Biology and Cancer Immunology, King's College London, London, UK.
  • Iannitto ML; Peter Gorer Department of Immunobiology, King's College London, London, UK.
  • Morton C; St. John's Institute of Dermatology, Guy's Hospital, London, UK.
  • Haque Y; Peter Gorer Department of Immunobiology, King's College London, London, UK.
  • Martin H; Peter Gorer Department of Immunobiology, King's College London, London, UK.
  • Biswas D; Peter Gorer Department of Immunobiology, King's College London, London, UK.
  • Ndagire S; Department of Medical Oncology, Guy's Hospital, London, UK.
  • Munonyara M; Peter Gorer Department of Immunobiology, King's College London, London, UK.
  • Gillett C; Immunosurveillance Laboratory, Francis Crick Institute, London, UK.
  • O'Neill O; Academic Foundation Programme, King's College Hospital, London, UK.
  • Nussbaumer O; King's Health Partners Cancer Biobank, Guy's Hospital, London, UK.
  • Hayday A; Department of Cellular Pathology, St. Thomas' Hospital, London, UK.
  • Wu Y; King's Health Partners Cancer Biobank, Guy's Hospital, London, UK.
Nat Cancer ; 5(3): 420-432, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38172341
ABSTRACT
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 αß T cells that ordinarily show PD-1-dependent exhaustion, it can also be efficacious against cancers evading αß 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+ αß 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Subgrupos de Linfocitos T / Neoplasias Límite: Humans Idioma: En Revista: Nat Cancer Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Subgrupos de Linfocitos T / Neoplasias Límite: Humans Idioma: En Revista: Nat Cancer Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido