Tumor-Associated Monocytes Reprogram CD8+ T Cells into Central Memory-Like Cells with Potent Antitumor Effects.
Adv Sci (Weinh)
; 11(16): e2304501, 2024 Apr.
Article
in En
| MEDLINE
| ID: mdl-38386350
ABSTRACT
CD8+ T cells are critical for host antitumor responses, whereas persistent antigenic stimulation and excessive inflammatory signals lead to T cell dysfunction or exhaustion. Increasing early memory T cells can improve T cell persistence and empower T cell-mediated tumor eradication, especially for adoptive cancer immunotherapy. Here, it is reported that tumor-associated monocytes (TAMos) are highly correlated with the accumulation of CD8+ memory T cells in human cancers. Further analysis identifies that TAMos selectively reprogram CD8+ T cells into T central memory-like (TCM-like) cells with enhanced recall responses. L-NMMA, a pan nitric oxide synthase inhibitor, can mitigate TAMo-mediated inhibition of T cell proliferation without affecting TCM-like cell generation. Moreover, the modified T cells by TAMo exposure and L-NMMA treatment exhibit long-term persistence and elicit superior antitumor effects in vivo. Mechanistically, the transmembrane protein CD300LG is involved in TAMo-mediated TCM-like cell polarization in a cell-cell contact-dependent manner. Thus, the terminally differentiated TAMo subset (CD300LGhighACElow) mainly contributes to TCM-like cell development. Taken together, these findings establish the significance of TAMos in boosting T-cell antitumor immunity.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Monocytes
/
CD8-Positive T-Lymphocytes
Limits:
Animals
/
Humans
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: