Relationship between the expression of PD-L1 and 18 F-FDG uptake in pancreatic ductal adenocarcinoma

Background PD-L1 promotes glycolysis in tumour cells. We observed a correlation between high PD-L1 expression and high 18 F-FDG uptake in patients with pancreatic ductal adenocarcinoma (PDAC) in a previous study. This study aims to determine the usefulness of 18 F-FDG PET/CT for evaluating the PD-L1 status in PDAC and to elucidate its rationality by integrated analyses. Methods For bioinformatics analysis, WGCNA, GSEA and TIMER were applied to analyse the pathways and hub genes associated with PD-L1 and glucose uptake. 18 F-FDG uptake assay was used to determine the glucose uptake rate of PDAC cells in vitro. Related genes expression were verified by RT-PCR and western blot. A retrospective analysis was performed on 47 patients with PDAC who had undergone 18 F-FDG PET/CT. Maximum standardised uptake values (SUV max ) were determined. The usefulness of SUV max for evaluating PD-L1 status was determined by receiver operating characteristic (ROC) curve analysis. Results Bioinformatics analysis showed that several signalling pathways are associated with both PD-L1 expression and tumour glucose uptake, among which JAK-STAT may be an important one. By in vitro experiments, the regulatory role of PD-L1 on glucose uptake was demonstrated, and its dependency on the JAK-STAT pathway was also verified by the rescue study. The SUV max of PD-L1-positive patients was significantly higher than PD-L1-negative in tumour cells (TCs) (6.1 ± 2.3 vs. 11.1 ± 4.2; P < 0.001), and in tumour-infiltrating immune cells (TIICs) (6.4 ± 3.2 vs. 8.4 ± 3.5; P < 0.001). In a multivariate analysis, SUV max was significantly associated with PD-L1 expression in TCs and TIICs ( P < 0.001 and P = 0.018, respectively). Using SUV max cut-off values of 8.15 and 7.75, PD-L1 status in TCs and TIICs could be predicted with accuracies of 91.5% and 74.5%, respectively. Conclusion Higher 18 F-FDG uptake by PDAC is associated with elevated PD-L1 expression. JAK-STAT is an important pathway that mediates PD-L1 to promote glucose uptake in PDAC.