Functional Reprogramming of Neutrophils within the Brain Tumor Microenvironment by Hypoxia-Driven Histone Lactylation.

ABSTRACT: Despite functional heterogeneity, the high frequency of intratumoral neutrophils predicts poor clinical outcomes. The tumor microenvironment reprograms neutrophils into immunosuppressive subsets that hinder anticancer immunity, thereby contributing to tumor growth and resistance to immunotherapies. However, the mechanisms underlying neutrophil reprogramming remain elusive. In this study, we report that the immunosuppressive ability of brain tumor-infiltrating neutrophils was restricted to a highly glycolytic and long-lived subset expressing CD71, which acquired immunosuppressive properties in response to hypoxia. Mechanistically, hypoxia boosted glucose metabolism in CD71+ neutrophils, leading to high lactate production. Lactate caused histone lactylation, which subsequently regulated argi

SUBMITTER: Ugolini A 

PROVIDER: S-EPMC12133432 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature