Membrane Cholesterol Efflux Drives Tumor-Associated Macrophage Reprogramming and Tumor Progression
Open accessAbstract
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 IFNγ-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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Ovarian tumor cells secrete some factor that upregulates ABCA1 and ABCG1 in macrophages, which then polarized them into a tumor-associated or M2-like state.
“Another report suggested that ovarian tumor cells secrete some factor that upregulates ABCA1 and ABCG1 in macrophages, which then polarized them into a tumor-associated or “M2-like” state (77).”
From Cholesterol efflux protein, ABCA1, supports anticancer functions of myeloid immune cells (2026) · cites this paper as [77]
The Discussion says ovarian cancer cells promote macrophage cholesterol efflux and TAM reprogramming, and suggests tumor-produced hyaluronan as a possible factor. But the Limitations section reports no increase in Abca1 or Abcg1 mRNA after exposure to tumor-cell conditioned medium; the mechanism increasing transporter activity remains unresolved. The claim therefore overstates the evidence by saying the factor upregulates ABCA1 and ABCG1. (LLM, conf=0.90)
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“Another report suggested that ovarian tumor cells secrete some factor that up-regulates ABCA1 and ABCG1 in macrophages, which then polarized them into a tumor-associated or “M2-like” state ( 89 ).”
- Authors
- Goossens, P., Rodriguez-Vita, J., Etzerodt, A., Masse, M., Rastoin, O., Gouirand, V., Ulas, T., Papantonopoulou, O., Van Eck, M., Auphan-Anezin, N., Bebien, M., Verthuy, C., Vu Manh, T. P., Turner, M., Dalod, M., Schultze, J. L., & Lawrence, T.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Bonn (DE)
- Babraham Institute (GB)
- Corresponding author
- Lawrence, Toby
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 29
- Issue
- 6
- Pages
- 1376-1389.e4
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2934055254
- Cited by
- 502
- References
- 8
- Citations by year
- 2026: 66 · 2025: 77 · 2024: 87 · 2023: 81 · 2022: 74 · 2021: 47 · 2020: 54 · 2019: 16
- FWCI
- 19.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- HAL (submittedVersion, cc-by-nc)
- HAL (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- bonndoc (University of Bonn) (submittedVersion)
- Research Portal (King's College London) (submittedVersion, cc-by-nc-nd)
- DZNE Pub (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- bonndoc (University of Bonn)
- Funders
- Centre National de la Recherche Scientifique
- European Research Council
- Novo Nordisk Fonden (NNF14OC0008781)
- Research Executive Agency (317445)
- Agence Nationale de la Recherche (ANR-09-MIEN-029-01, ANR-10-BLAN-1302-01)
- Institut National de la Santé et de la Recherche Médicale
- Ligue Contre le Cancer
- FP7 People: Marie-Curie Actions
- Seventh Framework Programme (260753)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- tumor-associated macrophages, macrophage polarization, lipid rafts, metastatic ovarian cancer, IL-4, interferon-gamma, ABC transporters, tumor microenvironment, immunosuppression, tumor progression, anti-tumor therapy
- MeSH terms
- Animals, Biological Transport, Bone Marrow Cells, Cell Membrane, Cells, Cultured, Cholesterol, Female, Macrophages, Mice, Inbred C57BL, Mice, Transgenic, Neoplasms, Disease Progression, ATP-Binding Cassette Transporters, Tumor Escape, Mice, Tumor Microenvironment, Cellular Reprogramming
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