Deterministic reprogramming of neutrophils within tumors

Deterministic reprogramming of neutrophils within tumors

Science

10.1126/science.adf6493

http://dx.doi.org/10.1126/science.adf6493

Melissa S. F. Ng, Immanuel Kwok, Leonard Tan, Changming Shi, Daniela Cerezo-Wallis, Yingrou Tan, Keith Leong, Gabriel F. Calvo, Katharine Yang, Yuning Zhang, Jingsi Jin, Ka Hang Liong, Dandan Wu, Rui He, Dehua Liu, Ye Chean Teh, Camille Bleriot, Nicoletta Caronni, Zhaoyuan Liu, Kaibo Duan, Vipin Narang, Iván Ballesteros, Federica Moalli, Mengwei Li, Jinmiao Chen, Yao Liu, Lianxin Liu, Jingjing Qi, Yingbin Liu, Lingxi Jiang, Baiyong Shen, Hui Cheng, Tao Cheng, Véronique Angeli, Ankur Sharma, Yuin-Han Loh, Hong Liang Tey, Shu Zhen Chong, Matteo Iannacone, Renato Ostuni, Andrés Hidalgo, Florent Ginhoux, Lai Guan Ng

11 January 2024

Ng, M. S. F., Kwok, I., Tan, L., Shi, C., Cerezo-Wallis, D., Tan, Y., Leong, K., Calvo, G. F., Yang, K., Zhang, Y., Jin, J., Liong, K. H., Wu, D., He, R., Liu, D., Teh, Y. C., Bleriot, C., Caronni, N., Liu, Z., … Ng, L. G. (2024). Deterministic reprogramming of neutrophils within tumors. Science, 383(6679). https://doi.org/10.1126/science.adf6493

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.

Publisher Copyright

This research / project is supported by the National Institutes of Health - NA
Grant Reference no. : R01AI165661

This research / project is supported by the Agency for Science, Technology and Research - Career Development Award
Grant Reference no. : C210112033

This research / project is supported by the Agency for Science, Technology and Research - Career Development Award
Grant Reference no. : C210112050

This research / project is supported by the Agency for Science, Technology and Research - Career Development Award
Grant Reference no. : 192D8043

This research / project is supported by the National Research Foundation - Shared Infrastructure Support
Grant Reference no. : NRF2017_SISFP09

This research / project is supported by the National Medical Research Council - Open Fund Individual Research Grant (OF-IRG)
Grant Reference no. : OFIRG19nov-0112

This research / project is supported by the National Medical Research Council - Clinician Scientist Award
Grant Reference no. : CSAINV20nov-0003

This research / project is supported by the National Medical Research Council - Clinician Scientist Award
Grant Reference no. : NMRC/CSA-INV/0023/2017

This research is supported by core funding from: Agency for Science, Technology and Research
Grant Reference no. : Singapore Immunology UIBR Award

This research / project is supported by the National Research Foundation - NRF Senior Investigatorship
Grant Reference no. : NRFI2017-02

This research is supported by core funding from: Singapore Immunology Network
Grant Reference no. : NA

This research work supported by 1) Italian Ministry for University and Research Grants - PRIN -2022FMESXL 2) Severo Ochoa Center of Excellence - CEX2020-001041-S 3) Leducq Foundation - TNE-18CVD04 4) Fundación La Caixa - HR17_00527 5) MCIN - RTI2018-095497-B-I00 6) Cancer Research Institute - CRI Irvington Postdoctoral Fellowship -CRI3511 7) BBVA Foundation - Leonardo Fellowship - LEO22-2-2596 8) MICINN - Ramon y Cajal Fellowship - RYC2021-033511-I 9) Italian Ministry for University and Research Grants - INF-ACT - PE00000007 10) Italian Association for Cancer Research - AIRC Grants - 22737 & 19891 11) Shanghai Science and Technology Commission - Science and Technology Innovation Plan Of Shanghai Science and Technology Commission - 20JC1410100 12) National Natural Science Foundation of China - 32270956 13) European Research Council - Proof of Concept Grants - 101138728 & 957502 14) European Research Council - Consolidator Grant - 725038 15) European Commission - 861878

This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science on VOL. 383, NO. 6679, 12 Jan 2024, DOI: 10.1126/science.adf6493

https://oar.a-star.edu.sg/communities-collections/articles/20347

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