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Unconventional human CD61 pairing with CD103 promotes TCR signaling and antigen-specific T cell cytotoxicity.
Hamid, Megat H B A; Cespedes, Pablo F; Jin, Chen; Chen, Ji-Li; Gileadi, Uzi; Antoun, Elie; Liang, Zhu; Gao, Fei; Teague, Renuka; Manoharan, Nikita; Maldonado-Perez, David; Khalid-Alham, Nasullah; Cerundolo, Lucia; Ciaoca, Raul; Hester, Svenja S; Pinto-Fernández, Adán; Draganov, Simeon D; Vendrell, Iolanda; Liu, Guihai; Yao, Xuan; Kvalvaag, Audun; Dominey-Foy, Delaney C C; Nanayakkara, Charunya; Kanellakis, Nikolaos; Chen, Yi-Ling; Waugh, Craig; Clark, Sally-Ann; Clark, Kevin; Sopp, Paul; Rahman, Najib M; Verrill, Clare; Kessler, Benedikt M; Ogg, Graham; Fernandes, Ricardo A; Fisher, Roman; Peng, Yanchun; Dustin, Michael L; Dong, Tao.
Afiliação
  • Hamid MHBA; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Cespedes PF; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Jin C; Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
  • Chen JL; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Gileadi U; Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • Antoun E; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Liang Z; MRC Translational Immune Discovery Unity, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Gao F; MRC Translational Immune Discovery Unity, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
  • Teague R; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Manoharan N; Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Maldonado-Perez D; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Khalid-Alham N; Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Cerundolo L; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Ciaoca R; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Hester SS; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • Pinto-Fernández A; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Draganov SD; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Vendrell I; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • Liu G; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, UK.
  • Yao X; Oxford National Institute of Health Research (NIHR) Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
  • Kvalvaag A; Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
  • Dominey-Foy DCC; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Nanayakkara C; Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Kanellakis N; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Chen YL; Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Waugh C; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Clark SA; Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Clark K; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Sopp P; Target Discovery Institute, Centre for Medicines Discovery, University of Oxford, Oxford, UK.
  • Rahman NM; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Verrill C; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Kessler BM; Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
  • Ogg G; Department of Molecular Cell Biology, Institute of Cancer Research, Oslo University Hospital, Oslo, Norway.
  • Fernandes RA; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Fisher R; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Peng Y; CAMS Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
  • Dustin ML; Oxford National Institute of Health Research (NIHR) Biomedical Research Centre, John Radcliffe Hospital, Oxford, UK.
  • Dong T; Laboratory of Pleural and Lung Cancer Translational Research, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
Nat Immunol ; 25(5): 834-846, 2024 May.
Article em En | MEDLINE | ID: mdl-38561495
ABSTRACT
Cancer remains one of the leading causes of mortality worldwide, leading to increased interest in utilizing immunotherapy strategies for better cancer treatments. In the past decade, CD103+ T cells have been associated with better clinical prognosis in patients with cancer. However, the specific immune mechanisms contributing toward CD103-mediated protective immunity remain unclear. Here, we show an unexpected and transient CD61 expression, which is paired with CD103 at the synaptic microclusters of T cells. CD61 colocalization with the T cell antigen receptor further modulates downstream T cell antigen receptor signaling, improving antitumor cytotoxicity and promoting physiological control of tumor growth. Clinically, the presence of CD61+ tumor-infiltrating T lymphocytes is associated with improved clinical outcomes, mediated through enhanced effector functions and phenotype with limited evidence of cellular exhaustion. In conclusion, this study identified an unconventional and transient CD61 expression and pairing with CD103 on human immune cells, which potentiates a new target for immune-based cellular therapies.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apirase / Receptores de Antígenos de Linfócitos T / Transdução de Sinais / Antígenos CD / Cadeias alfa de Integrinas Limite: Animals / Humans Idioma: En Revista: Nat Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Reino Unido
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apirase / Receptores de Antígenos de Linfócitos T / Transdução de Sinais / Antígenos CD / Cadeias alfa de Integrinas Limite: Animals / Humans Idioma: En Revista: Nat Immunol Assunto da revista: ALERGIA E IMUNOLOGIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Reino Unido