Deterministic reprogramming of neutrophils within tumors

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…

• EC
  European Commission

  Award: 861878
• NR
  National Research Foundation

  Award: NRF2017_SISFP09
• FL
  Fondation Leducq

  Award: TNE-18CVD04
• CN
  Centro Nacional de Investigaciones Cardiovasculares

  Award: CEX2020-001041-S
• NI
  National Institutes of Health
• MR
  Medical Research Council
• NM
  National Medical Research Council

  Awards: NMRC/CSA-INV/0023/2017, CSAINV20nov-0003