Abstract
1252
Objectives: Lung cancer is the malignant tumor with the highest incidence and mortality in China, among which lung adenocarcinoma is the most common pathological type. Currently, surgery, chemotherapy and molecular targeted therapy are the main treatment choices for lung adenocarcinoma. But most patients were diagnosed in late stage of disease, lost the opportunity of surgery and suffered the resistance to chemotherapy and targeted therapy, leading to a low overall survival rate. Immune escape has been considered crucial in tumor resistance and progression, which could be acquired by the inhibition of immune cells proliferation and function through the binding of Programmed death-ligand 1 (PD-L1) expressed by tumor cells to Programmed death-1 (PD-1) expressed by immune cells. Multiple mechanisms were involved in the immune escape of tumors. Studies have shown that tumor immune escape was closely related to tumor glucose metabolism reprogramming. The purpose of this study was to explore the mechanism of the impact of PD-L1 on the tumor glucose metabolism.
Methods: Lewis and La795 lung adenocarcinoma cell lines were selected. PD-L1 expression was upregulated by PD-L1 plasmid and downregulated by PD-L1 antibody. Western blot was used to detect the expression of PD-L1, phosphorylated serine / threonine kinase (p-Akt), Glucose transporter 1(GLUT1), Hexokinase 2(HK2) when PD-L1 was upregulated by plasmid, upregulated by plasmid with subsequent phosphatidylinositol 3-kinase (PI3K) / Akt pathway inhibition and downregulated by PD-L1 antibody, separately. The change of uptake of 18F-Fluorodeoxyglucose (18F-FDG) was detected by γ-counter and the change of glucose metabolism products was evaluated by detecting lactate in the medium under different interventions towards PD-L1. Results: The protein expression of PD-L1,p-Akt, GLUT1 and HK2 were increased after upregulation of PD-L1 in Lewis cell line and LA795 cell line; The uptake of 18F-FDG and the content of lactate in the medium were elevated after upregulation of PD-L1 and the difference was statistically significant (P <0.05); The protein expression of PD-L1,p-Akt, GLUT1 and HK2 were decreased when upregulated PD-L1 was subsequent given PI3K/ Akt pathway inhibition. The uptake of 18F-FDG and the content of lactate in the medium were decreased as well (P <0.05). The protein expression of PD-L1, p-Akt, GLUT1 and HK2 were decreased when PD-L1 was downregulated by PD-L1 antibody. The uptake of 18F-FDG and the content of lactate in the medium were also decreased (P <0.05). Conclusions: The expression of PD-L1 was related to the glucose metabolism. Glucose metabolism can be regulated by PD-L1 via PI3K/Akt pathway in lung adenocarcinoma. Upregulation or downregulation of PD-L1 can affect the expression of glycolysis-related enzymes/proteins, the glucose uptake and lactate production.
