Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties.
Nat Cancer
; 5(5): 791-807, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38228835
ABSTRACT
Brain tumors in children are a devastating disease in a high proportion of patients. Owing to inconsistent results in clinical trials in unstratified patients, the role of immunotherapy remains unclear. We performed an in-depth survey of the single-cell transcriptomes and clonal relationship of intra-tumoral T cells from children with brain tumors. Our results demonstrate that a large fraction of T cells in the tumor tissue are clonally expanded with the potential to recognize tumor antigens. Such clonally expanded T cells display enrichment of transcripts linked to effector function, tissue residency, immune checkpoints and signatures of neoantigen-specific T cells and immunotherapy response. We identify neoantigens in pediatric brain tumors and show that neoantigen-specific T cell gene signatures are linked to better survival outcomes. Notably, among the patients in our cohort, we observe substantial heterogeneity in the degree of clonal expansion and magnitude of T cell response. Our findings suggest that characterization of intra-tumoral T cell responses may enable selection of patients for immunotherapy, an approach that requires prospective validation in clinical trials.
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Linfócitos T
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article