CD8+ T cell activation in cancer comprises an initial activation phase in lymph nodes followed by effector differentiation within the tumor.
Immunity
; 56(1): 107-124.e5, 2023 01 10.
Article
in En
| MEDLINE
| ID: mdl-36580918
ABSTRACT
Improvements in tumor immunotherapies depend on better understanding of the anti-tumor T cell response. By studying human tumor-draining lymph nodes (TDLNs), we found that activated CD8+ T cells in TDLNs shared functional, transcriptional, and epigenetic traits with TCF1+ stem-like cells in the tumor. The phenotype and TCR overlap suggested that these TDLN cells were precursors to tumor-resident stem-like CD8+ T cells. Murine tumor models revealed that tumor-specific CD8+ T cells were activated in TDLNs but lacked an effector phenotype. These stem-like cells migrated into the tumor, where additional co-stimulation from antigen-presenting cells drove effector differentiation. This model of CD8+ T cell activation in response to cancer is different from that of canonical CD8+ T cell activation to acute viruses, and it proposes two stages of tumor-specific CD8+ T cell activation initial activation in TDLNs and subsequent effector program acquisition within the tumor after additional co-stimulation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
CD8-Positive T-Lymphocytes
/
Neoplasms
Limits:
Animals
/
Humans
Language:
En
Journal:
Immunity
Journal subject:
ALERGIA E IMUNOLOGIA
Year:
2023
Document type:
Article
Affiliation country:
United States