Neutrophil profiling illuminates anti-tumor antigen-presenting potency
Copyright © 2024 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:187 |
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| Enthalten in: |
Cell - 187(2024), 6 vom: 14. März, Seite 1422-1439.e24 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Yingcheng [VerfasserIn] |
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| Links: |
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| Themen: |
Antigen-presenting |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 19.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.cell.2024.02.005 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369373367 |
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| 520 | |a 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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| 700 | 1 | |a Nan, Fang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Tiancheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Shuyi |e verfasserin |4 aut | |
| 700 | 1 | |a Rao, Dongning |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Ke |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Xixi |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Guohe |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Jiaomeng |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Mao |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Yanan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shu |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Yihui |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Xiaoying |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Li |e verfasserin |4 aut | |
| 700 | 1 | |a Fan, Jia |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xiaoming |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Qiang |e verfasserin |4 aut | |
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