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How sugar instigates macrophages to be evils in tumor

Cellular & Molecular Immunology volume 19, pages 1325–1327 (2022)Cite this article

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In a recent issue of the journal Cancer Cell, Shi et al. reported that glucose metabolism remodels pro-tumoral functions of tumor-associated macrophages (TAMs) to support cancer metastasis and chemoresistance. Mechanistically, the consumption of glucose fuels hexosamine biosynthetic pathway (HBP) and enhances O-GlcNAcylation of Cathepsin B in macrophages, which upon secretion disrupts the tumor microenvironment (TME) [1].

Cancer progression occurs as the immune cells lose their ability to eliminate or control the outgrowth of malignant tumor cells. The dysfunction of the immune system can result from limited antigen recognition, immune suppression, as well as functional remodeling of immune cells [2]. To immune cells, the forced metabolic adaptation and nutrient competition with cancer cells determine their differentiation and function in TME. Of the immune cells in the tumor, macrophages and their precursors account for the largest fraction in the majority of human and murine solid malignancies. TAMs represent the highly dynamic and heterogeneous macrophage population across tumors, which acquire a unique spectrum of phenotypic, metabolic, and functional profiles in response to microenvironmental conditions. Based on the classical polarization model, TAMs can be defined as M1-like (pro-inflammatory and usually anti-tumoral) and M2-like (anti-inflammatory and pro-tumoral). M2-like TAMs have been observed to promote tumor growth, metastasis, angiogenesis, and chemoresistance. However, both M1-like and M2-like TAM subsets can co-exist in the same tumor, reflecting the fact that TAMs can be exposed to a variety of microenvironmental conditions in the tumor [3]. Therefore, it is an urgent question to understand how specific nutrients or signals in TME reshape and maintain the M2-like TAMs, and what is the mechanism of M2-like TAM-mediated cancer progression.

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Acknowledgements

This work was supported in part by grants from the Shenzhen Institute of Advanced Technology (HX) and the National Natural Science Foundation of China (No. 32130040) (YHC).

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  1. Center for Cancer Immunology, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Houjun Xia & Youhai H. Chen

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  1. Houjun Xia
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Correspondence to Houjun Xia or Youhai H. Chen.

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Xia, H., Chen, Y.H. How sugar instigates macrophages to be evils in tumor. Cell Mol Immunol 19, 1325–1327 (2022). https://doi.org/10.1038/s41423-022-00932-8

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