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Lactic acid in macrophage polarization: The significant role in inflammation and cancer

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INTERNATIONAL REVIEWS OF IMMUNOLOGY
卷 41, 期 1, 页码 4-18

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TAYLOR & FRANCIS INC
DOI: 10.1080/08830185.2021.1955876

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资金

  1. National Natural Science Foundation of China [21772080]
  2. Innovation Team Project Foundation of The Central University [31920200015]

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Lactic acid has been found to serve as a signal molecule with regulatory functions in immune system, metabolism, and polarization of macrophages. It can prevent excessive inflammatory responses during inflammation and promote tumor progression in malignant tumors through the polarization of tumor-associated macrophages. Targeting lactic acid may provide new strategies for the treatment of inflammation and cancer.
Metabolite lactic acid has always been regarded as a metabolic by-product rather than a bioactive molecule. Recently, this view has changed since it was discovered that lactic acid can be used as a signal molecule and has novel signal transduction functions both intracellular and extracellular, which can regulate key functions in the immune system. In recent years, more and more evidence has shown that lactic acid is closely related to the metabolism and polarization of macrophages. During inflammation, lactic acid is a regulator of macrophage metabolism, and it can prevent excessive inflammatory responses; In malignant tumors, lactic acid produced by tumor tissues promotes the polarization of tumor-associated macrophages, which in turn promotes tumor progression. In this review, we examined the relationship between lactic acid and macrophage metabolism. We further discussed how lactic acid plays a role in maintaining the homeostasis of macrophages, as well as the biology of macrophage polarization and the M1/M2 imbalance in human diseases. Potential methods to target lactic acid in the treatment of inflammation and cancer will also be discussed so as to provide new strategies for the treatment of diseases.

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