Metabolic Reprogramming Induces Macrophage Polarization in the Tumor Microenvironment

Abstract

Macrophages are one of the most important cells in the innate immune system, they are converted into two distinct subtypes with completely different molecular phenotypes and functional features under different stimuli of the microenvironment: M1 macrophages induced by IFN-γ/lipopolysaccharides(LPS) and M2 macrophages induced by IL-4/IL-10/IL-13. Tumor-associated macrophages (TAMs) differentiate from macrophages through various factors in the tumor microenvironment (TME). TAMs have the phenotype and function of M2 macrophages and are capable of secreting multiple cytokines to promote tumor progression. Both tumor cells and macrophages can meet the energy needs for rapid cell growth and proliferation through metabolic reprogramming, so a comprehensive understanding of pro-tumor and antitumor metabolic switches in TAM is essential to understanding immune escape mechanisms. This paper focuses on the functions of relevant signaling pathways and cytokines during macrophage polarization and metabolic reprogramming, and briefly discusses the effects of different microenvironments and macrophage pathogenicity, in addition to describing the research progress of inhibitory drugs for certain metabolic and polarized signaling pathways.

Molecular and Cellular Mechanisms of Propolis and Its Polyphenolic Compounds against Cancer

“…It has a crucial role in tumor growth as it supplies oxygen and nutrients that sustain the rapid and uncontrolled proliferation of cancer cells. The process of angiogenesis is usually required for tumors whose size is beyond 1–2 mm 3 and is predominantly stimulated by the vascular endothelial growth factor (VEGF) [ 341 , 342 , 343 ]. It is known that ROS regulates angiogenesis and tumor growth through VEGF.…”

“…It is known that ROS regulates angiogenesis and tumor growth through VEGF. Both tumor and stromal cells may release proangiogenic factors, such as VEGF, which promote the formation and maintenance of new vessels [ 70 , 341 , 342 ]. It is well-known that the cancer microenvironment, consisting of stromal, endothelial, immune, and cancer cells, is very important for carcinogenesis.…”

“…Our findings also suggested that CA may activate macrophages to secrete factors that regulate the function of T cells and other cells of the immune system [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. As explained previously, macrophages are one of the major cells of innate immunity with pivotal roles in the primary response to tumor cells, preservation of tissue homeostasis, inflammation, and immunity [ 70 , 341 , 342 , 343 ]. Besides their important role in killing tumor cells, they can be involved in tumor growth.…”

“…Besides their important role in killing tumor cells, they can be involved in tumor growth. In particular, M1 macrophages possess anticancer activity, whereas M2 macrophages and related TAMs promote tissue repair and remodeling, angiogenesis, and tumor growth [ 341 , 342 , 343 ].…”

Immune checkpoint inhibitors in osteosarcoma: A hopeful and challenging future

“…To avoid severe tissue and organ impairment caused by M1 macrophages, M2 macrophages, which are induced by IL-4/ IL-10/IL-13, are designed to exert anti-inflammatory, profibrotic and proangiogenic effects (Wang et al, 2022). The switch from M1 macrophages to M2 macrophages is called polarization (Zhao et al, 2022).…”