Deterministic reprogramming of neutrophils within tumors

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...

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Veröffentlicht in:	Science (American Association for the Advancement of Science) Jg. 383; H. 6679; S. eadf6493
Hauptverfasser:	Ng, Melissa S F, Kwok, Immanuel, Tan, Leonard, Shi, Changming, Cerezo-Wallis, Daniela, Tan, Yingrou, Leong, Keith, Calvo, Gabriel F, Yang, Katharine, Zhang, Yuning, Jin, Jingsi, Liong, Ka Hang, Wu, Dandan, He, Rui, Liu, Dehua, Teh, Ye Chean, Bleriot, Camille, Caronni, Nicoletta, Liu, Zhaoyuan, Duan, Kaibo, Narang, Vipin, Ballesteros, Iván, Moalli, Federica, Li, Mengwei, Chen, Jinmiao, Liu, Yao, Liu, Lianxin, Qi, Jingjing, Liu, Yingbin, Jiang, Lingxi, Shen, Baiyong, Cheng, Hui, Cheng, Tao, Angeli, Veronique, Sharma, Ankur, Loh, Yuin-Han, Tey, Hong Liang, Chong, Shu Zhen, Iannacone, Matteo, Ostuni, Renato, Hidalgo, Andrés, Ginhoux, Florent, Ng, Lai Guan
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 12.01.2024
Schlagworte:	Cellular Reprogramming - genetics Cellular Reprogramming - immunology Epigenesis, Genetic Humans Hypoxia Neoplasms - blood supply Neoplasms - immunology Neovascularization, Pathologic - genetics Neovascularization, Pathologic - immunology Neutrophils - immunology Proteomics Receptors, TNF-Related Apoptosis-Inducing Ligand - immunology Transcription, Genetic
ISSN:	1095-9203, 1095-9203
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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1095-9203 1095-9203
DOI:	10.1126/science.adf6493