PKM2 Drives Hepatocellular Carcinoma Progression by Inducing Immunosuppressive Microenvironment

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2020 Nov 16

PMID 33193421

Citations 36

Authors

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

Affiliations

Soon will be listed here.

Abstract

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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