Neutrophil profiling illuminates anti-tumor antigen-presenting potency.
Cell
; 187(6): 1422-1439.e24, 2024 Mar 14.
Article
em En
| MEDLINE
| ID: mdl-38447573
ABSTRACT
Neutrophils, the most abundant and efficient defenders against pathogens, exert opposing functions across cancer types. However, given their short half-life, it remains challenging to explore how neutrophils adopt specific fates in cancer. Here, we generated and integrated single-cell neutrophil transcriptomes from 17 cancer types (225 samples from 143 patients). Neutrophils exhibited extraordinary complexity, with 10 distinct states including inflammation, angiogenesis, and antigen presentation. Notably, the antigen-presenting program was associated with favorable survival in most cancers and could be evoked by leucine metabolism and subsequent histone H3K27ac modification. These neutrophils could further invoke both (neo)antigen-specific and antigen-independent T cell responses. Neutrophil delivery or a leucine diet fine-tuned the immune balance to enhance anti-PD-1 therapy in various murine cancer models. In summary, these data not only indicate the neutrophil divergence across cancers but also suggest therapeutic opportunities such as antigen-presenting neutrophil delivery.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Apresentação de Antígeno
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Neoplasias
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Neutrófilos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2024
Tipo de documento:
Article