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

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…

• AC
  American Cancer Society

  Award: IRG-21-145-25
• BA
  Ben and Catherine Ivy Foundation
• NI
  National Institute of Neurological Disorders and Stroke

  Award: R01 NS131912