Deterministic reprogramming of neutrophils within tumors.
Science
; 383(6679): eadf6493, 2024 01 12.
Article
en En
| MEDLINE
| ID: mdl-38207030
ABSTRACT
Neutrophils are increasingly recognized as key players in the tumor immune response and are associated with poor clinical outcomes. Despite recent advances characterizing the diversity of neutrophil states in cancer, common trajectories and mechanisms governing the ontogeny and relationship between these neutrophil states remain undefined. Here, we demonstrate that immature and mature neutrophils that enter tumors undergo irreversible epigenetic, transcriptional, and proteomic modifications to converge into a distinct, terminally differentiated dcTRAIL-R1+ state. Reprogrammed dcTRAIL-R1+ neutrophils predominantly localize to a glycolytic and hypoxic niche at the tumor core and exert pro-angiogenic function that favors tumor growth. We found similar trajectories in neutrophils across multiple tumor types and in humans, suggesting that targeting this program may provide a means of enhancing certain cancer immunotherapies.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Reprogramación Celular
/
Neoplasias
/
Neovascularización Patológica
/
Neutrófilos
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2024
Tipo del documento:
Article
País de afiliación:
Singapur