期刊
ONCOIMMUNOLOGY
卷 5, 期 12, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/2162402X.2016.1229725
关键词
Cytokines; epigenetics; immunometabolism; lactate; thyroid cancer; tumor-associated macrophages
资金
- ERC Consolidator Grant [310372]
- People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7 under REA [317445]
Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment in non-medullary thyroid cancer (TC), the most common endocrine malignancy. However, little is known regarding the regulation of their function in TC. Transcriptome analysis in a model of TC-induced macrophages identified increased inflammatory characteristics and rewiring of cell metabolism as key functional changes. This functional reprogramming was partly mediated by TC-derived lactate that induced upregulation of cytokine production through an AKT1/mTOR-dependent increase in aerobic glycolysis. This led to epigenetic modifications at the level of histone methylation, and subsequently long-term functional changes. Immunohistochemistry assessment validated the increase in glycolysis enzymes and lactate receptor in TAMs in tissue samples from patients with TC. In conclusion, Akt/mTOR-dependent glycolysis mediates TC-induced reprogramming of TAMs and inflammation, and this may represent a novel therapeutic target in TC.
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