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Intratumoral antigen signaling traps CD8+ T cells to confine exhaustion to the tumor site.
- Source :
- Science Immunology; 2024, Vol. 9 Issue 95, p1-13, 13p
- Publication Year :
- 2024
-
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<superscript>+</superscript> T cells in the tumor. These clonal populations expand and become increasingly exhausted over time. By contrast, antigen-signaled regulatory T cell (T<subscript>reg</subscript>) clonal populations readily recirculate out of the tumor. Consequently, intratumoral antigen signaling acts as a gatekeeper to compartmentalize CD8<superscript>+</superscript> T cell responses, even within the same clonotype, thus enabling exhausted T cells to remain confined to a specific tumor tissue site. Editor's summary: An understanding of how T cells behave after antigen signaling is critical to improving immunotherapies. Takahashi et al. developed the antigen receptor signaling reporter (AgRSR) mice to fate-map T cells responding to antigen signals. In tumors, they showed that antigen engagement caused clonally expanded CD8 T cells to be retained within tumors, resulting in T cell exhaustion. Whereas antigen engagement of regulatory T cells (T<subscript>regs</subscript>) within tumors similarly induced clonal expansion, T<subscript>regs</subscript> were able to recirculate. These results provide insight into T cell behaviors that may limit antitumor responses and introduce a system for tracking adaptive immunity. —Christiana Fogg [ABSTRACT FROM AUTHOR]
- Subjects :
- T-cell exhaustion
REGULATORY T cells
CLONE cells
T cells
ANTIGENS
Subjects
Details
- Language :
- English
- ISSN :
- 24709468
- Volume :
- 9
- Issue :
- 95
- Database :
- Complementary Index
- Journal :
- Science Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 177778647
- Full Text :
- https://doi.org/10.1126/sciimmunol.ade2094