Hello Lisa Jen

Macrophages are capable of displaying very different and even opposing phenotypes, depending on the microenvironment they are embedded in. Activated macrophages are often classified into M1 (classical-activated macrophages) and M2 (alternative-activated macrophages) phenotype. In general, M1 macrophages foster inflammation response against invading pathogens and tumor cells, whereas M2 macrophages tend to exert an immune suppressive phenotype, favoring tissue repair and tumor progression. These two types of macrophages are distinct in their different markers, metabolic characteristics, and gene expression profiles.

Under normal conditions, naïve M0 macrophages get energy by efficiently employing OXPHOS. Whereas, polarized macrophages (M1 and M2) rely more on their characteristic metabolic signatures for energy prerequisite within the tissue microenvironment.

To uphold dramatic pro-inflammatory functions, M1 macrophages trigger energy expenditure by the magnified aerobic glycolysis and Pentose Phosphate Pathway (PPP) in conjunction with decreased OXPHOS and fatty acid oxidation (FAO). Glycolysis and PPP are fundamental for macrophage functional adjustments and preventing the body from harmful events within an exigent time.

On the other hand, M2 macrophages preferentially utilize FAO and OXPHOS to execute cellular behaviors and activities. Although some evidence demonstrated that FAO is typical for M2 polarization, researchers believe that M2 macrophages retain the same dependence on glycolysis and exhibit modest glucose consumption. Glucose can fuel fatty acid synthesis to support increased FAO in M2 macrophages, linking glycolysis, fatty acid synthesis, and FAO.

What are you referring to, are the TAMs (Tumor-Associated Macrophages). Macrophages infiltrating tumor tissues or populated in the microenvironment of solid tumors are defined as tumor-associated macrophages (TAMs). As a critical component of tumor microenvironment, TAMs affect tumor growth, tumor angiogenesis, immune regulation, metastasis, and chemoresistance. By producing growth factors, proteolytic enzymes, and various inhibitory immune checkpoint proteins in T cells, TAMs display implicated functions in regulating metastasis.

Researches have revealed that TAMs actually have higher glucose uptake and a high level of glycolytic metabolism similar to M1 macrophages to support their cytokine profiles and functions. Simultaneously, lactic acid released by glycolytic cancer cells into the tumor microenvironment also upregulates HIF-1α expression in TAMs responsible for increased glycolysis and M2-like state.

You may want to refer to the articles attached below. They may be helpful.

https://jhoonline.biomedcentral.com/articles/10.1186/s13045-019-0760-3#:~:text=Tumor%2Dassociated%20macrophages%20(TAMs),proteins%20release%20in%20T%20cells.

https://www.frontiersin.org/articles/10.3389/fimmu.2021.702580/full

Best.

Thank you very much. I have learned a lot.