Intratumoral antigen signaling traps CD8 + T cells to confine exhaustion to the tumor site.

Autor: Takahashi M; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK.; Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo 113-0033, Japan., So TY; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK.; University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK., Chamberlain-Evans V; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK., Hughes R; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK., Yam-Puc JC; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK., Kania K; University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK., Ruhle M; University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK., Mann T; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK., Schuijs MJ; University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK., Coupland P; University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK.; Altos Labs Cambridge Institute, Cambridge CB21 6GP, UK., Naisbitt D; Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3G, UK., Halim TYF; University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK., Lyons PA; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK., Lio P; Department of Computer Science and Technology, University of Cambridge, Cambridge CB3 0FD, UK., Roychoudhuri R; Department of Pathology, University of Cambridge, Cambridge, UK., Okkenhaug K; Department of Pathology, University of Cambridge, Cambridge, UK., Adams DJ; Experimental Cancer Genetics, Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK., Smith KGC; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.; Department of Medicine, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.; Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.; University of Melbourne, Parkville, VIC 3052, Australia., Jodrell DI; Department of Oncology, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK., Chapman MA; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK.; Department of Hematology, University of Cambridge, Cambridge CB2 0RE, UK., Thaventhiran JED; Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK.; University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK.
Jazyk: angličtina
Zdroj: Science immunology [Sci Immunol] 2024 May 24; Vol. 9 (95), pp. eade2094. Date of Electronic Publication: 2024 May 24.
DOI: 10.1126/sciimmunol.ade2094
Abstrakt: Immunotherapy advances have been hindered by difficulties in tracking the behaviors of lymphocytes after antigen signaling. Here, we assessed the behavior of T cells active within tumors through the development of the antigen receptor signaling reporter (AgRSR) mouse, fate-mapping lymphocytes responding to antigens at specific times and locations. Contrary to reports describing the ready egress of T cells out of the tumor, we find that intratumoral antigen signaling traps CD8 + T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (T reg ) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8 + T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site.
Databáze: MEDLINE