Tumor-associated macrophages restrict CD8+ T cell function through collagen deposition and metabolic reprogramming of the breast cancer microenvironment.
Nat Cancer
; 5(7): 1045-1062, 2024 Jul.
Article
em En
| MEDLINE
| ID: mdl-38831058
ABSTRACT
Tumor progression is accompanied by fibrosis, a condition of excessive extracellular matrix accumulation, which is associated with diminished antitumor immune infiltration. Here we demonstrate that tumor-associated macrophages (TAMs) respond to the stiffened fibrotic tumor microenvironment (TME) by initiating a collagen biosynthesis program directed by transforming growth factor-ß. A collateral effect of this programming is an untenable metabolic milieu for productive CD8+ T cell antitumor responses, as collagen-synthesizing macrophages consume environmental arginine, synthesize proline and secrete ornithine that compromises CD8+ T cell function in female breast cancer. Thus, a stiff and fibrotic TME may impede antitumor immunity not only by direct physical exclusion of CD8+ T cells but also through secondary effects of a mechano-metabolic programming of TAMs, which creates an inhospitable metabolic milieu for CD8+ T cells to respond to anticancer immunotherapies.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Colágeno
/
Linfócitos T CD8-Positivos
/
Microambiente Tumoral
/
Macrófagos Associados a Tumor
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nat Cancer
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Estados Unidos