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Impact of glucose metabolism on PD-L1 expression in sorafenib-resistant hepatocellular carcinoma cells.

ABSTRACT: Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for advanced HCC. However, several patients exhibit resistance to sorafenib during treatment. This study aimed to assess the effect of glucose deprivation on PD-L1 expression in HCC cells. We used PD-L1-overexpressing HepG2 cells and IFN-γ-treated SK-Hep1 cells to explore the impact of glycolysis on PD-L1 expression. To validate the correlation between PD-L1 expression and glycolysis, we analyzed data from The Cancer Genome Atlas (TCGA) and used immunostaining for HCC tissue analysis. Furthermore, to modulate PD-L1 expression, we treated HepG2, SK-Hep1, and sorafenib-resistant SK-Hep1R cells with rapamycin. Here, we found that glucose deprivation reduced PD-L1 expression in HCC cells. Additionally, TCGA data and immunostaining analyses confirmed a positive correlation between the expression of hexokinase II (HK2), which plays a key role in glucose metabolism, and PD-L1. Notably, rapamycin treatment decreased the expression of PD-L1 and HK2 in both high PD-L1-expressing HCC cells and sorafenib-resistant cells. Our results suggest that the modulation of PD-L1 expression by glucose deprivation may represent a strategy to overcome PD-L1 upregulation in patients with sorafenib-resistant HCC.

SUBMITTER: Cho S

PROVIDER: S-EPMC10798953 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Impact of glucose metabolism on PD-L1 expression in sorafenib-resistant hepatocellular carcinoma cells.

Cho Sua S Kim Wonjin W Yoo Dayoung D Han Yeonju Y Hwang Hyemin H Kim Seunghwan S Kim Jimin J Park Sanghee S Park Yusun Y Jo HanHee H Pyun Jae-Chul JC Lee Misu M

Scientific reports 20240119 1

Hepatocellular carcinoma (HCC) is the fifth leading cause of cancer-related mortality worldwide. Programmed cell death ligand-1 (PD-L1) is an immune checkpoint protein that binds to programmed cell death-1 (PD-1), which is expressed in activated T cells and other immune cells and has been employed in cancer therapy, including HCC. Recently, PD-L1 overexpression has been documented in treatment-resistant cancer cells. Sorafenib is a multikinase inhibitor and the only FDA-approved treatment for ad ...[more]

PMID: 38243049

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Dataset Information

Impact of glucose metabolism on PD-L1 expression in sorafenib-resistant hepatocellular carcinoma cells.

Publications

Impact of glucose metabolism on PD-L1 expression in sorafenib-resistant hepatocellular carcinoma cells.

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