Intratumoral antigen signaling traps CD8 <sup>+</sup> T cells to confine exhaustion to the tumor site-Reference-Cited by-同舟云学术

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

Published:2024-05-24 Issue:95 Volume:9 Page:
ISSN:2470-9468
Container-title:Science Immunology
language:en
Short-container-title:Sci. Immunol.

Author:

Takahashi Munetomo¹²^ORCID,So Tsz Y.¹³,Chamberlain-Evans Vitalina¹^ORCID,Hughes Robert¹,Yam-Puc Juan Carlos¹^ORCID,Kania Katarzyna³^ORCID,Ruhle Michelle³^ORCID,Mann Tiffeney¹^ORCID,Schuijs Martijn J.³^ORCID,Coupland Paul³⁴^ORCID,Naisbitt Dean⁵^ORCID,Halim Timotheus Y. F.³^ORCID,Lyons Paul A.⁶⁷^ORCID,Lio Pietro⁸^ORCID,Roychoudhuri Rahul⁹^ORCID,Okkenhaug Klaus⁹^ORCID,Adams David J.¹⁰^ORCID,Smith Ken G. C.⁶⁷¹¹¹²^ORCID,Jodrell Duncan I.¹³^ORCID,Chapman Michael A.¹¹⁴^ORCID,Thaventhiran James E. D.¹³^ORCID

Affiliation:

1. Medical Research Council Toxicology Unit, University of Cambridge, Gleeson Building, Tennis Court Road, Cambridge CB2 1QR, UK.

2. Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo 113-0033, Japan.

3. University of Cambridge, CRUK Cambridge Institute, Cambridge CB2 0RE, UK.

4. Altos Labs Cambridge Institute, Cambridge CB21 6GP, UK.

5. Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Building, Ashton Street, Liverpool L69 3G, UK.

6. Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, Cambridge, UK.

7. Department of Medicine, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, Cambridge, UK.

8. Department of Computer Science and Technology, University of Cambridge, Cambridge CB3 0FD, UK.

9. Department of Pathology, University of Cambridge, Cambridge, UK.

10. Experimental Cancer Genetics, Wellcome Sanger Institute, Hinxton, Cambridgeshire CB10 1SA, UK.

11. Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

12. University of Melbourne, Parkville, VIC 3052, Australia.

13. Department of Oncology, University of Cambridge, School of Clinical Medicine, Cambridge Biomedical Campus, Box 197, Cambridge CB2 0XZ, UK.

14. Department of Hematology, University of Cambridge, Cambridge CB2 0RE, UK.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/sciimmunol.ade2094

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