Intratumoral antigen signaling traps CD8+ T cells to confine exhaustion to the tumor site.
Sci Immunol
; 9(95): eade2094, 2024 May 24.
Article
in En
| MEDLINE
| ID: mdl-38787961
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 (Treg) 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.
Full text:
1
Database:
MEDLINE
Main subject:
Signal Transduction
/
CD8-Positive T-Lymphocytes
Limits:
Animals
Language:
En
Journal:
Sci Immunol
Year:
2024
Type:
Article
Affiliation country:
United kingdom