研究人员证明了进入肿瘤的未成熟和成熟的中性粒细胞会经历不可逆的表观遗传、转录和蛋白质组学修饰，从而汇聚成一种独特的终末分化的dcTRAIL-R1+状态。重编程的dcTRAIL-R1+中性粒细胞主要定位于肿瘤核心的糖酵解和缺氧微环境，并发挥有利于肿瘤生长的促血管生成功能。
研究人员在多种肿瘤类型和人体中发现了中性粒细胞的类似轨迹，这表明针对这一程序可能提供一种增强某些癌症免疫疗法的方法。
研究人员表示，中性粒细胞越来越被认为是肿瘤免疫反应的关键角色，并与不良的临床预后有关。尽管最近在描述癌症中性粒细胞状态的多样性方面取得了进展，但这些中性粒细胞状态之间的本体和关系的共同轨迹和机制仍未确定。
附：英文原文
Title: Deterministic reprogramming of neutrophils within tumors
Author: 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, Veronique Angeli, Ankur Sharma, Yuin-han Loh, Hong Liang Tey, Shu Zhen Chong, Matteo Iannacone, Renato Ostuni, Andrés Hidalgo, Florent Ginhoux, Lai Guan Ng
Issue&Volume: 2024-01-12
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.
DOI: adf6493
Source: https://www.science.org/doi/10.1126/science.adf6493