Please use this identifier to cite or link to this item:http://hdl.handle.net/20.500.12105/20369
Title
Deterministic reprogramming of neutrophils within tumors.
Author(s)
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
Date issued
2024-01-12
Citation
Science. 2024 Jan 12;383(6679):eadf6493.
Language
Inglés
Document type
journal article
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.
MESH
Neoplasms | Neutrophils | Cellular Reprogramming | Neovascularization, Pathologic | Humans | Proteomics | Receptors, TNF-Related Apoptosis-Inducing Ligand | Epigenesis, Genetic | Hypoxia | Transcription, Genetic
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