Deterministic reprogramming of neutrophils within tumors

被引：165

作者：

Ng, Melissa S. F. ^{[1
]}

Kwok, Immanuel ^{[1
]}

Tan, Leonard ^{[1
]}

Shi, Changming ^{[2
]}

Cerezo-Wallis, Daniela ^{[3
,4
,5
]}

Tan, Yingrou ^{[1
,6
]}

Leong, Keith ^{[1
]}

Calvo, Gabriel F. ^{[7
,8
]}

Yang, Katharine ^{[1
]}

Zhang, Yuning ^{[9
,10
]}

Jin, Jingsi ^{[2
]}

Liong, Ka Hang ^{[1
]}

Wu, Dandan ^{[11
]}

He, Rui ^{[2
]}

Liu, Dehua ^{[1
]}

Teh, Ye Chean ^{[1
]}

Bleriot, Camille ^{[12
,13
]}

Caronni, Nicoletta ^{[14
]}

Liu, Zhaoyuan ^{[11
]}

Duan, Kaibo ^{[1
]}

Narang, Vipin ^{[1
]}

Ballesteros, Ivan ^{[3
]}

Moalli, Federica ^{[15
,16
]}

Li, Mengwei ^{[1
]}

Chen, Jinmiao ^{[1
]}

Liu, Yao ^{[17
]}

Liu, Lianxin ^{[17
]}

Qi, Jingjing ^{[18
,19
]}

Liu, Yingbin ^{[18
,19
]}

Jiang, Lingxi ^{[20
,21
,22
]}

Shen, Baiyong ^{[20
,21
,22
]}

Cheng, Hui ^{[23
]}

Cheng, Tao ^{[23
]}

Angeli, Veronique ^{[9
,10
]}

Sharma, Ankur ^{[24
,25
,26
]}

Loh, Yuin-han ^{[27
]}

Tey, Hong Liang ^{[6
,28
,29
]}

Chong, Shu Zhen ^{[1
,30
]}

Iannacone, Matteo ^{[15
,16
,31
]}

Ostuni, Renato ^{[14
,31
]}

Hidalgo, Andres ^{[3
,4
,5
]}

Ginhoux, Florent ^{[1
,11
,12
,32
]}

Ng, Lai Guan ^{[1
,2
,30
]}

机构：

[1] ASTAR, Singapore Immunol Network SIgN, Singapore, Singapore

[2] Shanghai Jiao Tong Univ, Shanghai Immune Therapy Inst, Renji Hosp, Sch Med, Shanghai, Peoples R China

[3] Ctr Nacl Invest Cardiovasc Carlos III, Area Cell & Dev Biol, Madrid, Spain

[4] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, New Haven, CT USA

[5] Yale Univ, Sch Med, Dept Immunobiol, New Haven, CT USA

[6] Natl Healthcare Grp, Natl Skin Ctr, Singapore, Singapore

[7] Univ Castilla La Mancha, Dept Math, Ciudad Real, Spain

[8] Univ Castilla La Mancha, MOLAB Math Oncol Lab, Ciudad Real, Spain

[9] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Microbiol & Immunol, Immunol Translat Res Program, Singapore, Singapore

[10] Natl Univ Singapore, Life Sci Inst, Immunol Program, Singapore, Singapore

[11] Shanghai Jiao Tong Univ, Sch Med, Shanghai Inst Immunol, Shanghai, Peoples R China

[12] Inst Gustave Roussy, INSERM, U1015, Villejuif, France

[13] Inst Necker Enfants Malades, CNRS, UMR8253, Paris, France

[14] IRCCS San Raffaele Sci Inst, San Raffaele Telethon Inst Gene Therapy SR Tiget, Genom Innate Immune Syst Unit, Milan, Italy

[15] IRCCS San Raffaele Sci Inst, Div Immunol Transplantat & Infect Dis, Milan, Italy

[16] IRCCS San Raffaele Sci Inst, Expt Imaging Ctr, Milan, Italy

[17] Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Hepatobiliary Surg, Div Life Sci & Med, Hefei, Anhui, Peoples R China

[18] Shanghai Jiao Tong Univ, Renji Hosp, Dept Biliary & Pancreat Surg, Sch Med, Shanghai, Peoples R China

[19] Shanghai Jiao Tong Univ, Shanghai Inst Canc Biol, Renji Hosp, Sch Med, Shanghai, Peoples R China

[20] Shanghai Jiao Tong Univ, Ruijin Hosp, Dept Gen Surg, Pancreat Dis Ctr,Sch Med, Shanghai, Peoples R China

[21] Shanghai Jiao Tong Univ, Res Inst Pancreat Dis, Shanghai Key Lab Translat Res Pancreat Neoplasms, Sch Med, Shanghai, Peoples R China

[22] Shanghai Jiao Tong Univ, Inst Translat Med, State Key Lab Oncogenes & Related Genes, Shanghai, Peoples R China

[23] Chinese Acad Med Sci & Peking Union Med Coll, Inst Hematol & Blood Dis Hosp, Natl Clin Res Ctr Blood Dis, State Key Lab Expt Hematol,Haihe Lab Cell Ecosyst, Tianjin, Peoples R China

[24] Harry Perkins Inst Med Res, QEII Med Ctr, Nedlands, WA, Australia

[25] Curtin Univ, Curtin Med Sch, Bentley, WA, Australia

[26] Curtin Univ, Curtin Hlth Innovat Res Inst, Bentley, WA, Australia

[27] A STAR Agcy Sci Res & Technol, Inst Mol & Cell Biol IMCB, Singapore, Singapore

[28] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore, Singapore

[29] Natl Univ Singapore, Yong Loo Lin Sch Med, Singapore, Singapore

[30] Natl Univ Singapore, Dept Microbiol & Immunol, Singapore, Singapore

[31] Univ Vita Salute San Raffaele, Milan, Italy

[32] SingHealth Duke NUS Acad Med Ctr, Translat Immunol Inst, Singapore, Singapore

来源：

SCIENCE | 2024年 / 383卷 / 6679期

基金：

英国医学研究理事会; 新加坡国家研究基金会; 中国国家自然科学基金; 欧洲研究理事会;

关键词：

SUPPRESSOR-CELLS; PROGENITOR; RESISTANCE; PLASTICITY; EXPANSION; REVEALS; MODEL; MOUSE; VEGF;

D O I：

10.1126/science.adf6493

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：163 / +

页数：17

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