Metabolic reprogramming in macrophage responses

Abstract

Macrophages are critical mediators of tissue homeostasis, with the function of tissue development and repair, but also in defense against pathogens. Tumor-associated macrophages (TAMs) are considered as the main component in the tumor microenvironment and play an important role in tumor initiation, growth, invasion, and metastasis. Recently, metabolic studies have revealeded specific metabolic pathways in macrophages are tightly associated with their phenotype and function. Generally, pro-inflammatory macrophages (M1) rely mainly on glycolysis and exhibit impairment of the tricarboxylic acid (TCA) cycle and mitochondrial oxidative phosphorylation (OXPHOS), whereas anti-inflammatory macrophages (M2) are more dependent on mitochondrial OXPHOS. However, accumulating evidence suggests that macrophage metabolism is not as simple as previously thought. This review discusses recent advances in immunometabolism and describes how metabolism determines macrophage phenotype and function. In addition, we describe the metabolic characteristics of TAMs as well as their therapeutic implications. Finally, we discuss recent obstacles facing this area as well as promising directions for future study.

Glucose Metabolism: The Metabolic Signature of Tumor Associated Macrophage

“…On the other hand, glycolysis also supplies glucose-6-phosphate to the PPP, provoking the production of nicotinamide adenine dinucleotide phosphate (NADPH) and ribose-5-phosphate. Though glycolysis possesses a lower capacity for ATP generation than OXPHOS, (only two ATP per molecule of glucose), it is a more rapid source of energy for macrophages and other cells and contributes metabolic intermediates for biosynthetic pathways to support the synthesis of ribose, amino acids, and fatty acids that are crucial for metabolic adaptation ( 22 , 23 ). Apart from the above-mentioned three glucose metabolism pathways, glucose can further be metabolized via the hexosamine biosynthesis pathway (HBP) (2–5%) and eventually leading to the generation of a donor molecule uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) ( 24 – 26 ).…”

Dynamic Evaluation of Circulating miRNA Profile in EGFR-Mutated NSCLC Patients Treated with EGFR-TKIs

“…Although cel-miR-39 has been extensively used as a normalizer for circulating miRNA quantification, spike-in controls cannot normalize variations caused by factors prior to RNA isolation [ 39 ]. In addition, modulation of miR-21 might not only characterize cancer cells, but also be a common feature of pathological cell growth, as observed in mouse models with hypertrophic heart and other non-neoplastic diseases [ 40 , 41 ]. In this sense, we excluded a putative influence of comorbidities on miRNA circulating levels in our cohort of patients.…”

Circulating Tumor Cell Persistence Associates with Long-Term Clinical Outcome to a Therapeutic Cancer Vaccine in Prostate Cancer

“…The expression of PD-L1 on CTCs has been linked to tumor immune evasion [ 10 ]. In the present study, Gleason grade and IF markers were correlated.…”

“…Relative quantification of serum proteins known to be implicated in the interplay between the immune system and tumorigenic processes was performed by proximity extension assay (PEA) technology (Olink Bioscience Service Center Uppsala, Uppsala, Sweden) [ 10 ]. Briefly, one microliter serum drawn at study inclusion was profiled by the Immuno-Oncology panel (v.1).…”