Self-Maintaining CD103 + Cancer-Specific T Cells Are Highly Energetic with Rapid Cytotoxic and Effector Responses.

Autor:	Abd Hamid M; Chinese Academy of Medical Sciences (CAMS) Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Colin-York H; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Khalid-Alham N; Institute of Biomedical Engineering, Department of Engineering Science, University of Oxford, Oxford, United Kingdom.; Oxford National Institute of Health Research (NIHR) Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom., Browne M; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom., Cerundolo L; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom., Chen JL; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Yao X; Chinese Academy of Medical Sciences (CAMS) Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Rosendo-Machado S; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Waugh C; Flow Cytometry Facility, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom., Maldonado-Perez D; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom., Bowes E; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom., Verrill C; Oxford National Institute of Health Research (NIHR) Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.; Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom., Cerundolo V; Chinese Academy of Medical Sciences (CAMS) Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Conlon CP; Chinese Academy of Medical Sciences (CAMS) Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Fritzsche M; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.; Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom., Peng Y; Chinese Academy of Medical Sciences (CAMS) Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom., Dong T; Chinese Academy of Medical Sciences (CAMS) Oxford Institute, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom. tao.dong@imm.ox.ac.uk.; Medical Research Council (MRC) Human Immunology Unit, MRC Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2020 Feb; Vol. 8 (2), pp. 203-216. Date of Electronic Publication: 2019 Nov 26.
DOI:	10.1158/2326-6066.CIR-19-0554
Abstrakt:	Enrichment of CD103 + tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103 + cytotoxic CD8 + T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103 + CTLs by assessing T-cell receptor (TCR)-matched CD103 + and CD103 - cancer-specific CTL immunity in vitro and its immunophenotype ex vivo Interestingly, we found that differentiated CD103 + cancer-specific CTLs expressed the active form of TGFβ1 to continually self-regulate CD103 expression, without relying on external TGFβ1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103 + CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103 + cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies. (©2019 American Association for Cancer Research.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu