Deterministic reprogramming of neutrophils within tumors

• 成果类型: Article
• 署名作者: 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, Ivan; 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, Andres; Ginhoux, Florent; Ng, Lai Guan
• 署名单位: Agency for Science Technology & Research (A*STAR); A*STAR - Singapore Immunology Network (SIgN); Shanghai Jiao Tong University; Centro Nacional de Investigaciones Cardiovasculares (CNIC); Yale University; Yale University; National Skin Centre; Universidad de Castilla-La Mancha; Universidad de Castilla-La Mancha; National University of Singapore; National University of Singapore; Shanghai Jiao Tong University; Chinese Academy of Sciences; UNICANCER; Gustave Roussy; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Saclay; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); CNRS - National Institute for Biology (INSB); Fondazione Telethon; San Raffaele Telethon Institute For Gene Therapy (Sr-Tiget); Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Vita-Salute San Raffaele University; IRCCS Ospedale San Raffaele; Chinese Academy of Sciences; University of Science & Technology of China, CAS; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Shanghai Jiao Tong University; Chinese Academy of Medical Sciences - Peking Union Medical College; Institute of Hematology & Blood Diseases Hospital - CAMS; Peking Union Medical College; Queen Elizabeth II Medical Centre; Harry Perkins Institute of Medical Research; University of Western Australia; Curtin University; Curtin University; Agency for Science Technology & Research (A*STAR); A*STAR - Institute of Molecular & Cell Biology (IMCB); Nanyang Technological University; National University of Singapore; National University of Singapore; Vita-Salute San Raffaele University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11025
• DOI: 10.1126/science.adf6493
• 发表日期: 2024-01-12
• 页码: 163-+
• 关键词: suppressor-cells; progenitor; resistance; plasticity; expansion; reveals; MODEL; mouse; vegf

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.