Deterministic Reprogramming of Neutrophils Within Tumors

Overview

Journal Science

Specialty Science

Date 2024 Jan 11

PMID 38207030

Authors

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

Ivan 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

Andres Hidalgo

Florent Ginhoux

Lai Guan Ng

Affiliations

Soon will be listed here.

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.

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