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 CCK-8, colony formation, and transwell assays, and 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 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 proliferation, migration, and invasion of HCC cells, as well as 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7606949 | PMC |
| http://dx.doi.org/10.3389/fimmu.2020.589997 | DOI Listing |
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