Polarization State of Macrophages Under Lactate Action

Sixuan Li

doi:10.62051/pzrb9h17

Authors

Sixuan Li

DOI:

https://doi.org/10.62051/pzrb9h17

Keywords:

lactic acid; M1 macrophages; M2 macrophages; mechanism of action.

Abstract

As the most prevalent immunological population in the tumor microenvironment (TME), tumor associated macrophages (TAMs) are crucial to TME. Simultaneously, acidic environment is a prominent feature in TME. Recent studies have shown that macrophages undergo further division into two distinct types of TAMs, namely M1 and M2, respectively. They are induced by different inducing factors and play different roles in cancer and inflammation. Lactic acid strongly enhances the transformation of macrophages with M1 designation into macrophages with the M2 designation, as shown by the increased expression of M2 genes. This article analyzes EC lactate and obtains the results of its transportation in the form of MCT1 lactate transporter. There is also an epigenetic mechanism that promotes macrophage polarization. Using lactate as a target, MCT1 inhibitor AZD3965 can inhibit the expression of M2 macrophages. Because it only discusses lactic acid in acidic environments, it has limitations. This article provides reference for future research on lactate, and the specific mechanism of action of HIF-1 α in lactate environment has not been resolved. Future research can focus on this direction.

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References

[1] Feng R, Morine Y, Ikemoto T, et al. Nrf2 activation drives macrophages polarization and cancer cell epithelial-mesenchymal transition during interaction. Cell Communication and Signaling, 2018, 16(1): 54.

[2] Ohashi T, Aoki M, Tomita H, et al. M2-like macrophage polarization in high lactic acid-producing head and neck cancer. Cancer Science, 2017, 108(6): 1128-1134.

[3] Zhang L, Li S. Lactic acid promotes macrophage polarization through MCT-HIF1α signaling in gastric cancer. Experimental Cell Research, 2020, 388(2): 111846.

[4] Boutilier AJ, Elsawa SF. Macrophage Polarization States in the Tumor Microenvironment. International Journal of Molecular Sciences, 2021, 22(13): 6995.

[5] Wang F, Zhang S, Jeon R, et al. Interferon Gamma Induces Reversible Metabolic Reprogramming of M1 Macrophages to Sustain Cell Viability and Pro-Inflammatory Activity. EBioMedicine, 2018, 30: 303-316.

[6] Huang X, Li Y, Fu M, et al. Polarizing Macrophages In Vitro[M]. In: Rousselet G. (eds) Macrophages. Methods in Molecular Biology, vol 1784. New York: Humana Press, 2018.

[7] Zhou D, Huang C, Lin Z, et al. Macrophage polarization and function with emphasis on the evolving roles of coordinated regulation of cellular signaling pathways. Cell Signaling, 2014, 26(2): 192-197.

[8] Ziemba AM, D'Amato AR, MacEwen TM, et al. Stabilized Interleukin-4-Loaded Poly(lactic-co-glycolic) Acid Films Shift Proinflammatory Macrophages toward a Regenerative Phenotype in Vitro. ACS Applied Bio Materials, 2019, 2(4): 1498-1508.

[9] Shapouri-Moghaddam A, Mohammadian S, Vazini H, et al. Macrophage plasticity, polarization, and function in health and disease. Journal of Cellular Physiology, 2018, 233(9): 6425-6440.

[10] Galván-Peña S, O'Neill LA. Metabolic reprograming in macrophage polarization. Frontiers in Immunology, 2014, 5: 420.

[11] Ippolito L, Morandi A, Giannoni E, et al. Lactate: A Metabolic Driver in the Tumour Landscape. Trends in Biochemical Sciences, 2019, 44(2): 153-166.

[12] Zhou HC, Xin-Yan Y, Yu WW, et al. Lactic acid in macrophage polarization: The significant role in inflammation and cancer. International Reviews of Immunology, 2022, 41(1): 4-18.

[13] Colegio OR, Chu NQ, Szabo AL, et al. Functional polarization of tumour-associated macrophages by tumour-derived lactic acid. Nature, 2014, 513(7519): 559-563.

[14] Zhang J, Muri J, Fitzgerald G, et al. Endothelial Lactate Controls Muscle Regeneration from Ischemia by Inducing M2-like Macrophage Polarization. Cell Metabolism, 2020, 31(6): 1136-1153.e7.

[15] Zhang D, Tang Z, Huang H, et al. Metabolic regulation of gene expression by histone lactylation. Nature, 2019, 574(7779): 575-580.

[16] Silva A, Antunes B, Batista A, et al. In Vivo Anticancer Activity of AZD3965: A Systematic Review. Molecules, 2021, 27(1): 181.