dc.contributor.author | Ng, Melissa S F | |
dc.contributor.author | Kwok, Immanuel | |
dc.contributor.author | Tan, Leonard | |
dc.contributor.author | Shi, Changming | |
dc.contributor.author | Cerezo-Wallis, Daniela | |
dc.contributor.author | Tan, Yingrou | |
dc.contributor.author | Leong, Keith | |
dc.contributor.author | Calvo, Gabriel F | |
dc.contributor.author | Yang, Katharine | |
dc.contributor.author | Zhang, Yuning | |
dc.contributor.author | Jin, Jingsi | |
dc.contributor.author | Liong, Ka Hang | |
dc.contributor.author | Wu, Dandan | |
dc.contributor.author | He, Rui | |
dc.contributor.author | Liu, Dehua | |
dc.contributor.author | Teh, Ye Chean | |
dc.contributor.author | Bleriot, Camille | |
dc.contributor.author | Caronni, Nicoletta | |
dc.contributor.author | Liu, Zhaoyuan | |
dc.contributor.author | Duan, Kaibo | |
dc.contributor.author | Narang, Vipin | |
dc.contributor.author | Ballesteros, Iván | |
dc.contributor.author | Moalli, Federica | |
dc.contributor.author | Li, Mengwei | |
dc.contributor.author | Chen, Jinmiao | |
dc.contributor.author | Liu, Yao | |
dc.contributor.author | Liu, Lianxin | |
dc.contributor.author | Qi, Jingjing | |
dc.contributor.author | Liu, Yingbin | |
dc.contributor.author | Jiang, Lingxi | |
dc.contributor.author | Shen, Baiyong | |
dc.contributor.author | Cheng, Hui | |
dc.contributor.author | Cheng, Tao | |
dc.contributor.author | Angeli, Veronique | |
dc.contributor.author | Sharma, Ankur | |
dc.contributor.author | Loh, Yuin-Han | |
dc.contributor.author | Tey, Hong Liang | |
dc.contributor.author | Chong, Shu Zhen | |
dc.contributor.author | Iannacone, Matteo | |
dc.contributor.author | Ostuni, Renato | |
dc.contributor.author | Hidalgo, Andrés | |
dc.contributor.author | Ginhoux, Florent | |
dc.contributor.author | Ng, Lai Guan | |
dc.date.accessioned | 2024-07-09T15:09:26Z | |
dc.date.available | 2024-07-09T15:09:26Z | |
dc.date.issued | 2024-01-12 | |
dc.identifier.citation | Science. 2024 Jan 12;383(6679):eadf6493. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/20369 | |
dc.description.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. | es_ES |
dc.description.sponsorship | This
research was funded by Singapore Immunology Network (SIgN)
core funding and A*STAR, Singapore. L.G.N. is supported by
National Natural Science Foundation of China (grant 32270956)
and Shanghai Science and Technology Commission (grant
20JC1410100). M.S.F. is supported by the A*STAR Career
Development Fund (grant 202D8150). I.W.K. is supported by the
A*STAR Career Development Fund (grant 202D8197). S.Z.C. is
supported by the A*STAR Career Development Award (192D8043)
and core funding from SIgN. Y.T. and H.L.T. are supported by
Clinician Scientist Awards (NMRC/CSA-INV/0023/2017 and
CSAINV20nov-0003) from the National Medical Research Council
of Singapore. The SIgN Flow Cytometry facility is supported by
National Research Foundation (NRF) Singapore under Shared
Infrastructure Support (SIS) (NRF2017_SISFP09). For the use of
the Ultramicroscope II, we would like to thank A*STAR core funds,
the HMBS IAF-PP grant (H1701a0004), and the National
Research Foundation’s Shared Infrastructure Support grant for
SingaScope, a Singapore-wide microscopy infrastructure network
(NRF2017_SISFP10), for continued support of the A*STAR
Microscopy Platform. D.C.-W. is supported by a CRI Irvington
postdoctoral fellowship (CRI3511). G.F.C. is supported by grant
PID2022-142341OB-I00 funded by the Spanish MCIN/AEI/
10.13039/501100011033. I.B. is supported by a Ramon y Cajal
fellowship (RYC2021-033511-I) from MICINN and by a Leonardo
fellowship (LEO22-2-2596) from the BBVA Foundation. A.V.
and Y.Z. are supported by NMRC OF-IRG grant to VA (OFIRG19nov-0112).
M.I. is supported by the European Research Council (ERC)
Consolidator Grant 725038, ERC Proof of Concept Grants 957502
and 101138728, Italian Association for Cancer Research (AIRC)
Grants 19891 and 22737, Italian Ministry for University and
Research Grants PE00000007 (INF-ACT) and PRIN (2022FMESXL),
and by a Funded Research Agreement from Asher Biotherapeutics
and VIR Biotechnology. A.H. is supported by grant R01AI165661 from
NIH/NIAD, RTI2018-095497- B-I00 from MCIN, HR17_00527 from
Fundación La Caixa, the Transatlantic Network of Excellence
(TNE-18CVD04) from the Leducq Foundation, and FET-OPEN
(grant 861878) from the European Commission. The CNIC is supported
by the MCIN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). F.G. is supported by
Singapore Immunology UIBR award from the Agency for Science,
Technology and Research (A*STAR), a Singapore NRF Senior
Investigatorship (NRFI2017-02), the Fondation Gustave Roussy, and
the ARC Foundation. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Association for the Advancement of Science (AAAS) | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Neoplasms | es_ES |
dc.subject.mesh | Neutrophils | es_ES |
dc.subject.mesh | Cellular Reprogramming | es_ES |
dc.subject.mesh | Neovascularization, Pathologic | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Proteomics | es_ES |
dc.subject.mesh | Receptors, TNF-Related Apoptosis-Inducing Ligand | es_ES |
dc.subject.mesh | Epigenesis, Genetic | es_ES |
dc.subject.mesh | Hypoxia | es_ES |
dc.subject.mesh | Transcription, Genetic | es_ES |
dc.title | Deterministic reprogramming of neutrophils within tumors. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 38207030 | es_ES |
dc.format.volume | 383 | es_ES |
dc.format.number | 6679 | es_ES |
dc.format.page | eadf6493 | es_ES |
dc.identifier.doi | 10.1126/science.adf6493 | es_ES |
dc.contributor.funder | Singapore Immunology Network | es_ES |
dc.contributor.funder | National Natural Science Foundation of China | es_ES |
dc.contributor.funder | Shanghai Science and Technology Commission | es_ES |
dc.contributor.funder | National Medical Research Council of Singapore | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Fundación BBVA | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.contributor.funder | Fondation Leducq | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1095-9203 | es_ES |
dc.relation.publisherversion | 10.1126/science.adf6493 | es_ES |
dc.identifier.journal | Science (New York, N.Y.) | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Imagen de la Inflamación Cardiovascular y la Respuesta Inmune | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/ERC/CoG/725038 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/ERC/957502 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/ERC/101138728 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2022-142341OB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/MCIN/AEI/10.13039/501100011033 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RYC2021-033511-I | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/LEO22-2-2596 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2018-095497- B-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR17/00527 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/CEX2020-001041-S | es_ES |