Distinct spatiotemporal dynamics of CD8+ T cell-derived cytokines in the tumor microenvironment.
Cancer Cell
; 42(1): 157-167.e9, 2024 01 08.
Article
em En
| MEDLINE
| ID: mdl-38194914
ABSTRACT
Cells in the tumor microenvironment (TME) influence each other through secretion and sensing of soluble mediators, such as cytokines and chemokines. While signaling of interferon γ (IFNγ) and tumor necrosis factor α (TNFα) is integral to anti-tumor immune responses, our understanding of the spatiotemporal behavior of these cytokines is limited. Here, we describe a single cell transcriptome-based approach to infer which signal(s) an individual cell has received. We demonstrate that, contrary to expectations, CD8+ T cell-derived IFNγ is the dominant modifier of the TME relative to TNFα. Furthermore, we demonstrate that cell pools that show abundant IFNγ sensing are characterized by decreased expression of transforming growth factor ß (TGFß)-induced genes, consistent with IFNγ-mediated TME remodeling. Collectively, these data provide evidence that CD8+ T cell-secreted cytokines should be categorized into local and global tissue modifiers, and describe a broadly applicable approach to dissect cytokine and chemokine modulation of the TME.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Citocinas
/
Fator de Necrose Tumoral alfa
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article