Table_1_PKM2 Drives Hepatocellular Carcinoma Progression by Inducing Immunosuppressive Microenvironment.docx (2.18 MB)
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Table_1_PKM2 Drives Hepatocellular Carcinoma Progression by Inducing Immunosuppressive Microenvironment.docx

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posted on 20.10.2020, 04:54 by Tian-En Li, Shun Wang, Xiao-Tian Shen, Ze Zhang, Mo Chen, Hao Wang, Ying Zhu, Da Xu, Bei-Yuan Hu, Ran Wei, Yan Zheng, Qiong-Zhu Dong, Lun-Xiu Qin
Background and Aims

Pyruvate kinase M2 (PKM2) is an essential regulator of the Warburg effect, but its biological function promoting immune escape of hepatocellular carcinoma (HCC) is unclear.

Methods

GEPIA web tool and immunohistochemistry (IHC) analysis were employed to evaluate the clinical relevance of PKM2 in HCC patients. Both in vitro CCK-8, colony formation, and transwell assays, and in vivo xenografts were performed to evaluate the malignancy of HCC cells. PKM2 and PD-L1 levels were examined by Western blot, qRT-PCR, and IHC. The role of PKM2 on in vivo immune response was also investigated.

Results

PKM2 was significantly upregulated in HCC and associated with a poor prognosis of HCC patients. Knockdown of PKM2 inhibited in vitro proliferation, migration, and invasion of HCC cells, as well as in vivo tumor growth. Strikingly, PKM2 showed a strong correlation with the expression of immune inhibitory cytokines and lymphocyte infiltration in HCC. The overexpression of PKM2 sensitized HCC to immune checkpoint blockade, which enhanced IFN-γ positive CD8 T cells in HCC mice models.

Conclusion

PKM2 might be a predictor and a potential therapeutic target for immune checkpoint inhibitors in HCC.

History

References