Understanding and reversing mammary tumor-driven reprogramming of myelopoiesis to reduce metastatic spread

Tumor-induced systemic accumulation and polarization of neutrophils to an immunosuppressive phenotype is a potent driver of metastasis formation. Yet, how mammary tumors reprogram granulopoiesis at the molecular level and when tumor imprinting occurs during neutrophil development remains underexplored. Here, we combined single-cell, chromatin and functional analyses to unravel the tumor-driven reprogramming of granulopoiesis in the bone marrow, along with intervention studies aimed at reversing this process. We observe that mammary tumors accelerate commitment to the neutrophil lineage at the expense of lymphopoiesis and erythropoiesis without stimulating the development of a novel myeloid lineage. Moreover,…

• MV
  Ministerie van Volksgezondheid, Welzijn en Sport
• NO
  Nederlandse Organisatie voor Wetenschappelijk Onderzoek

  Awards: 91819616, VI.C.222.049
• KK
  KWF Kankerbestrijding

  Award: KWF14801
• OI
  Oncode Institute
• ER
  European Research Council

  Awards: KWF13191, 615300, 14339 KWF/Oncode, 865459