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PKM2 Drives Hepatocellular Carcinoma Progression by Inducing Immunosuppressive Microenvironment
- Source :
- Frontiers in Immunology, Frontiers in Immunology, Vol 11 (2020)
- Publication Year :
- 2020
-
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 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.
- Subjects :
- 0301 basic medicine
Male
B7-H1 Antigen
Mice
0302 clinical medicine
Tumor Microenvironment
Immunology and Allergy
Cytotoxic T cell
Immune Checkpoint Inhibitors
Original Research
Mice, Inbred BALB C
biology
Liver Neoplasms
hepatocellular carcinoma
Prognosis
Warburg effect
Hepatocellular carcinoma
Disease Progression
lcsh:Immunologic diseases. Allergy
PD-L1
Thyroid Hormones
Carcinoma, Hepatocellular
Immunology
Mice, Nude
PKM2
Cell Line
03 medical and health sciences
Immune system
In vivo
medicine
Immune Tolerance
Animals
Humans
neoplasms
business.industry
immunosuppressive microenvironment
immune escape
Membrane Proteins
medicine.disease
Immune checkpoint
digestive system diseases
Mice, Inbred C57BL
030104 developmental biology
biology.protein
Cancer research
progression
pyruvate kinase M2
lcsh:RC581-607
business
Carrier Proteins
030215 immunology
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in immunology
- Accession number :
- edsair.doi.dedup.....b3a7760c095b503b962370eeae0315f5