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Deterministic reprogramming of neutrophils within tumors.

Melissa Shu Feng NgImmanuel KwokLeonard TanChang-Ming ShihDaniela Cerezo-WallisYingrou TanKeith Weng Kit LeongGabriel F CalvoKatharine Lu YangYuning ZhangJingsi JinKa Hang LiongDandan WuRui HeDehua LiuYe Chean TehCamille BlériotNicoletta CaronniZhaoyuan LiuKaibo DuanVipin NarangIván BallesterosFederica MoalliMengwei LiJinmiao ChenYao LiuLian-Xin LiuJingjing QiYingbin LiuLingxi JiangBaiyong ShenHui ChengTao ChengVeronique AngeliAnkur SharmaYuin-Han LohHong Liang TeyShu Zhen ChongMatteo IannaconeRenato OstuniAndrés HidalgoFlorent GinhouxLai Guan Ng
Published in: Science (New York, N.Y.) (2024)
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.
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