Distinct phenotypic states and spatial distribution of CD8+ T cell clonotypes in human brain metastases.
Cell Rep Med
; 3(5): 100620, 2022 05 17.
Article
em En
| MEDLINE
| ID: mdl-35584630
ABSTRACT
Metastatic disease in the brain is difficult to control and predicts poor prognosis. Here, we analyze human brain metastases and demonstrate their robust infiltration by CD8+ T cell subsets with distinct antigen specificities, phenotypic states, and spatial localization within the tumor microenvironment. Brain metastases are densely infiltrated by T cells; the majority of infiltrating CD8+ T cells express PD-1. Single-cell RNA sequencing shows significant clonal overlap between proliferating and exhausted CD8+ T cells, but these subsets have minimal clonal overlap with circulating and other tumor-infiltrating CD8+ T cells, including bystander CD8+ T cells specific for microbial antigens. Using spatial transcriptomics and spatial T cell receptor (TCR) sequencing, we show these clonally unrelated, phenotypically distinct CD8+ T cell populations occupy discrete niches within the brain metastasis tumor microenvironment. Together, our work identifies signaling pathways within CD8+ T cells and in their surrounding environment that may be targeted for immunotherapy of brain metastases.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Linfócitos T CD8-Positivos
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article