AUTHOR=Li Tian-En , Wang Shun , Shen Xiao-Tian , Zhang Ze , Chen Mo , Wang Hao , Zhu Ying , Xu Da , Hu Bei-Yuan , Wei Ran , Zheng Yan , Dong Qiong-Zhu , Qin Lun-Xiu 

TITLE=PKM2 Drives Hepatocellular Carcinoma Progression by Inducing Immunosuppressive Microenvironment

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.589997

DOI=10.3389/fimmu.2020.589997

ISSN=1664-3224

ABSTRACT=<sec><title>Background and Aims</title><p>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.</p></sec><sec><title>Methods</title><p>GEPIA web tool and immunohistochemistry (IHC) analysis were employed to evaluate the clinical relevance of PKM2 in HCC patients. Both <italic>in vitro</italic> CCK-8, colony formation, and transwell assays, and <italic>in vivo</italic> 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 <italic>in vivo</italic> immune response was also investigated.</p></sec><sec><title>Results</title><p>PKM2 was significantly upregulated in HCC and associated with a poor prognosis of HCC patients. Knockdown of PKM2 inhibited <italic>in vitro</italic> proliferation, migration, and invasion of HCC cells, as well as <italic>in vivo</italic> 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.</p></sec><sec><title>Conclusion</title><p>PKM2 might be a predictor and a potential therapeutic target for immune checkpoint inhibitors in HCC.</p></sec>