Single-cell meta-analyses reveal responses of tumor-reactive CXCL13+ T cells to immune-checkpoint blockade.
Nat Cancer
; 3(9): 1123-1136, 2022 09.
Article
em En
| MEDLINE
| ID: mdl-36138134
Immune-checkpoint blockade (ICB) therapies represent a paradigm shift in the treatment of human cancers; however, it remains incompletely understood how tumor-reactive T cells respond to ICB across tumor types. Here, we demonstrate that measuring CXCL13 expression could effectively identify both precursor and terminally differentiated tumor-reactive CD8+ T cells within tumors. Applying this approach, we performed meta-analyses of published single-cell data for CXCL13+CD8+ T cells in 225 samples from 102 patients treated with ICB across five cancer types. We found that CXCL13+CD8+ T cells were correlated with favorable responses to ICB, and the treatment further increased such cells in responsive tumors. In addition, CXCL13+ tumor-reactive subsets exhibited variable responses to ICB in distinct contexts, likely due to different degrees of exhaustion-related immunosuppression. Our integrated analyses provide insights into mechanisms underlying ICB and suggest that bolstering precursor tumor-reactive CD8+ T cells might provide an effective therapeutic approach to improve cancer treatment.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD8-Positivos
/
Neoplasias
Tipo de estudo:
Prognostic_studies
/
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Nat Cancer
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China