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Article Dans Une Revue Cell Metabolism Année : 2019

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

Martin Turner
Marc Dalod
Toby Lawrence

Résumé

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 IL-4-mediated reprogramming, including inhibition of IFN gamma-induced gene expression. Genetic deletion of ABC transporters, which mediate cholesterol efflux, reverts the tumor-promoting functions of TAMs and reduces tumor progression. These studies reveal an unexpected role for membrane-cholesterol efflux in driving TAM-mediated tumor progression while pointing to a potentially novel anti-tumor therapeutic strategy.
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Dates et versions

hal-02359441 , version 1 (25-10-2021)

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Paternité - Pas d'utilisation commerciale

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Pieter Goossens, Juan Rodriguez-Vita, Anders Etzerodt, Marion Massé, Olivia Rastoin, et al.. Membrane Cholesterol Efflux Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression. Cell Metabolism, 2019, 29 (6), pp.1376-1389. ⟨10.1016/j.cmet.2019.02.016⟩. ⟨hal-02359441⟩
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