Effects of glycolysis on the polarization and function of tumor‑associated macrophages (Review)

Abstract

Under conditions of oxygen sufficiency, tumor cells supply themselves with energy through glycolysis, which is one of the causes of their rapid proliferation, metastasis and acquisition of drug resistance. Tumor-associated macrophages (TAMs) are transformed from peripheral blood monocytes and are among the immune-related cells that constitute the tumor microenvironment (TME). Altered glycolysis levels in TAMs have an important impact on their polarization and function. The cytokines secreted by TAMs, and phagocytosis in different polarization states, affect tumorigenesis and development. Furthermore, changes in glycolysis activity of tumor cells and other immune-related cells in the TME also affect the polarization and function of TAMs. Studies on the relationship between glycolysis and TAMs have received increasing attention. The present study summarized the link between glycolysis of TAMs and their polarization and function, as well as the interaction between changes in glycolysis of tumor cells and other immune-associated cells in the TME and TAMs. The present review aimed to provide a comprehensive understanding of the effects of glycolysis on the polarization and function of TAMs. Contents 1. Introduction 2. Effects of altered glycolysis of TAMs on their own polarization and function 3. Effects of altered levels of glycolysis in tumor cells and other immune cells in the TME on TAM polarization and function 4. Problems and perspectives

Exosome-mediated communication between gastric cancer cells and macrophages: implications for tumor microenvironment

“…TAM is an essential part of TME in diverse tumors and plays a significant role in the genesis, progression, angiogenesis, and immunosuppression of abundant cancers ( 167 – 170 ). Furthermore, TAM infiltration, connected with the prognosis of many tumors, can be taken advantage of as a prognostic indicator and a novel therapeutic target for many tumors ( 171 – 173 ). As a result, further comprehension of the interaction of TAM with tumor cells and the specific mechanism of immunosuppression in TME can help optimize the therapeutic regimen, and disrupting the malignant interactions between TAM and tumor cells can benefit and inhibit tumor progression.…”

Analyzing the impact of metabolism on immune cells in tumor microenvironment to promote the development of immunotherapy

“…In TME, TAMs gather in hypoxic areas and quickly undergo glycolysis. In addition, TAMs can also secrete immunosuppressive cytokines, and vascular endothelial growth factors to promote tumor development ( 80 ). On the one hand, TAMs can promote tumor replication and invasion through colony-stimulating factor 1 and epidermal growth factor, on the other hand, they can express immunosuppressive factors like interleukin to facilitate the immune escape of tumor cells ( 81 ).…”

“…TAMs include M1-like macrophages and M2-like macrophages, and there are differences in their energy sources and metabolic patterns ( 45 ). Specifically, the energy source of M1-like macrophages is primarily glycolysis, while the energy of M2-like macrophages is mainly provided by fatty acid oxidation and oxidative phosphorylation ( 80 ). Interestingly, different types of macrophages have different metabolic patterns.…”

“…In lipid metabolism, while the fatty acids oxidation is adjusted downward in M1-like macrophages, it can be upregulated in M2-like macrophages induced by IL-4. Besides, the metabolic characteristics of arachidonic acid are different in these two types of macrophages ( 80 ). In M2-like macrophages, the content of cyclooxygenase 2 (COX2) is higher, and the content of cyclooxygenase 1 (COX1) is lower.…”

“…For instance, in TME, the glucose metabolism of TAMs has changed from oxidative phosphorylation to aerobic glycolysis, thus promoting the activation of M1-like TAM ( 61 ). Furthermore, lactic acid can facilitate the polarization of M2-like macrophages through many kinds of signaling pathways, including MCT1 and HIF-1, eventually promoting tumor development ( 80 ). In lipid metabolism, the metabolic mode of TAMs depends on the stage of the tumors and the requirements in the special environment ( 61 ).…”