Membrane Cholesterol Efflux Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression

Macrophages possess intrinsic tumoricidal activity, yet tumor-associated macrophages (TAMs) rapidly adopt an alternative phenotype within the tumor microenvironment that is marked by tumor-promoting immunosuppressive and trophic functions. The mechanisms that promote such TAM polarization remain poorly understood, but once identified, they may represent important therapeutic targets to block the tumor-promoting functions of TAMs and restore their anti-tumor potential. Here, we have characterized TAMs in a mouse model of metastatic ovarian cancer. We show that ovarian cancer cells promote membrane-cholesterol efflux and depletion of lipid rafts from macrophages. Increased cholesterol efflux promoted…

• AU
  Aix-Marseille Université
• AN
  Agence Nationale de la Recherche

  Awards: ANR-10-INBS-04-01, ANR-09-MIEN-029-01, ANR-10-BLAN-1302-01
• IN
  Institut National de la Santé et de la Recherche Médicale
• LC
  Ligue Contre le Cancer
• CN
  Centre National de la Recherche Scientifique
• NN
  Novo Nordisk Fonden

  Award: NNF14OC0008781
• NN
  Novo Nordisk Foundation Center for Basic Metabolic Research

  Award: NNF14OC0008781
• SF
  Seventh Framework Programme

  Award: 260753
• BA
  Biotechnology and Biological Sciences Research Council

  Awards: BBS/E/B/000C0428, BB/I01246X/1, BB/M021343/1
• ER
  European Research Council
• RE
  Research Executive Agency

  Award: 317445
• HE
  H2020 European Research Council

  Award: FP7/2007–2013
• FP
  FP7 People: Marie-Curie Actions