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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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) Vol. 383; no. 6679; p. eadf6493
Main Authors: 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
Language:English
Published: United States 12.01.2024
Subjects:
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
Online Access:Get more information
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Summary: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.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.adf6493