Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship

• Published in: Cancer letters Vol. 413; pp. 102 - 109
• Main Authors: Netea-Maier, Romana T., Smit, Johannes W.A., Netea, Mihai G.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 28-01-2018; Elsevier Limited
• Subjects: Adenosine triphosphate; Angiogenesis; Animals; Aquatic plants; Arachidonic acid; Byproducts; Cell metabolism; Cell Proliferation; Cues; Cytokines; Energy Metabolism; Genotype & phenotype; Glycolysis; Humans; Hypoxia; Immunometabolism; Inflammation; Inflammation Mediators - metabolism; Kinases; Lactic acid; Macrophages; Macrophages - immunology; Macrophages - metabolism; Macrophages - pathology; Medical prognosis; Metabolism; Metastases; Metastasis; Neoplasms - immunology; Neoplasms - metabolism; Neoplasms - pathology; Nitric oxide; Nitrogen cycle; Nutrients; Pancreatic cancer; Phenotype; Prostaglandins; Reactive oxygen species; Rodents; Signal Transduction; Tumor cells; Tumor Microenvironment; Tumor-associated macrophages; Tumors; Vascular endothelial growth factor; TAM; MDSC; LO; G3P; E-FABP; Gln; OXPHOS; F1,6P; TNF; HK2; HETE; CAIX; PI3K; RNS; PDK4; mTOR; iNOS; F6P; IL; ARG1; TCA; 2DG; ROS; FA; NK; TLR4; REDD1; NADPH; αKG; NO; Cell metabolism; acetyl CoA; Tumor-associated macrophages; LPS; IFN; PPP; MCT4; NADH; MCT1; SREBP1; G6P; GLUT1; PGE2; Tumor microenvironment; VEGF; Treg; FADH2; AKT; TME; COX; PPARs; NAD; Immunometabolism; TG; FAO; PDCA; ATP; DC; ETM
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2017.10.037

In order to adapt to the reduced availability of nutrients and oxygen in the tumor microenvironment and the increased requirements of energy and building blocks necessary for maintaining their high proliferation rate, malignant cells undergo metabolic changes that result in an increased production of lactate, nitric oxide, reactive oxygen species, prostaglandins and other byproducts of arachidonic acid metabolism that influence both the composition of the inflammatory microenvironment and the function of the tumor-associated macrophages (TAMs). In response to cues present in the TME, among which products of altered tumor cell metabolism, TAMs are also required to reprogram their metabolism, with activation of glycolysis, fatty acid synthesis and altered nitrogen cycle metabolism. These changes result in functional reprogramming of TAMs which includes changes in the production of cytokines and angiogenetic factors, and contribute to the tumor progression and metastasis. Understanding the metabolic changes governing the intricate relationship between the tumor cells and the TAMs represents an essential step towards developing novel therapeutic approaches targeting the metabolic reprogramming of the immune cells to potentiate their tumoricidal potential and to circumvent therapy resistance.
•To maintain a high proliferation rate cancer cells adapt their cellular metabolism.•This results in depletion of nutrients and release of toxic metabolites in the tumor microenvironment.•In response to tumor cells-derived metabolic cues TAMs undergo metabolic reprogramming.•Metabolic reprogramming of TAMs subsequently influences their functional phenotype.