J Cancer 2021; 12(12):3566-3574. doi:10.7150/jca.54430


Mechanism of PKM2 affecting cancer immunity and metabolism in Tumor Microenvironment

Mengxi Chen1#, Huan Liu1#, Zhang Li2, Alex Lau Ming2, Honglei Chen1,2✉

1. Department of Pathology, Zhongnan Hospital of Wuhan University, Wuhan 430071, P. R. China.
2. Department of Pathology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, P. R. China.
#The authors contributed equally to the present manuscript.

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Chen M, Liu H, Li Z, Ming AL, Chen H. Mechanism of PKM2 affecting cancer immunity and metabolism in Tumor Microenvironment. J Cancer 2021; 12(12):3566-3574. doi:10.7150/jca.54430. Available from https://www.jcancer.org/v12p3566.htm

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PKM2 is the enzyme that regulates the final rate-limiting step of glycolysis. PKM2 expression can reinforce the utilization of oxygen and synthesis of growth substances in cancer cells by enhancing OXPHOS and the Warburg effect. In cancer immunity, PKM2 can modulate the expression of PD-L1 in M2 macrophage and decrease the amount and activity of CD8+ T cells. This affects cancer cell killing and immune escape sequentially. How PKM2 regulates PD-L1 expression through immunometabolism is summarized. PKM2 builds a bridge between energy metabolism and cancer immunity. The activator and inhibitor of PKM2 both promote the anti-cancer immune response and inhibit cancer growth and metastasis by regulating the metabolism of cancer cells and immune cells in the tumor microenvironment through HIF-1α/PKM2 pathway. This review focuses on the precise role of PKM2 modulating immunometabolism, providing valuable suggestions for further study in this field.

Keywords: PKM-2, PD-L1, cancer immunity, metabolism