Enhanced lipid biosynthesis in human tumor-induced macrophages contributes to their protumoral characteristics
Publication year
2020Source
Journal for Immunotherapy of Cancer, 8, 2, (2020), article e000638ISSN
Publication type
Article / Letter to editor

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Organization
Internal Medicine
Radiation Oncology
Journal title
Journal for Immunotherapy of Cancer
Volume
vol. 8
Issue
iss. 2
Subject
Radboudumc 18: Healthcare improvement science RIHS: Radboud Institute for Health Sciences; Radboudumc 2: Cancer development and immune defence RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life Sciences; Radboudumc 9: Rare cancers RIMLS: Radboud Institute for Molecular Life SciencesAbstract
BACKGROUND: Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment (TME) in non-medullary thyroid carcinoma (TC) and neuroblastoma (NB), being associated with a poor prognosis for patients. However, little is known about how tumors steer the specific metabolic phenotype and function of TAMs. METHODS: In a human coculture model, transcriptome, metabolome and lipidome analysis were performed on TC-induced and NB-induced macrophages. The metabolic shift was correlated to functional readouts, such as cytokine production and reactive oxygen species (ROS) production, including pharmacological inhibition of metabolic pathways. RESULTS: Based on transcriptome and metabolome analysis, we observed a strong upregulation of lipid biosynthesis pathways in TAMs. Subsequently, lipidome analysis revealed that tumor-induced macrophages have an increased total lipid content and enriched levels of intracellular lipids, especially phosphoglycerides and sphingomyelins. Strikingly, this metabolic shift in lipid synthesis contributes to their protumoral functional characteristics: blocking key enzymes of lipid biosynthesis in the tumor-induced macrophages reversed the increased inflammatory cytokines and the capacity to produce ROS, two well-known protumoral factors in the TME. CONCLUSIONS: Taken together, our data show that tumor cells can stimulate lipid biosynthesis in macrophages to induce protumoral cytokine and ROS responses and advocate lipid biosynthesis as a potential therapeutic target to reprogram the TME.
This item appears in the following Collection(s)
- Academic publications [205116]
- Electronic publications [103350]
- Faculty of Medical Sciences [81054]
- Open Access publications [71830]
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