Tumor immunity is related to 18F-FDG uptake in thymic epithelial tumor

Background: 2-deoxy-2-[fluorine-18] fluoro-d-glucose (F-18-FDG) positron emission tomography (F-18-FDG-PET) is a convenient modality to assess the metabolic activity within tumor cells. However, there is no consensus regarding the relationship between F-18-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between F-18-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs. Methods A total of 108 patients with histologically confirmed TETs classified as thymomas or thymic carcinomas who underwent surgical resection or biopsy or needle biopsy and F-18-FDG PET before any treatment between August 2007 and March 2020 were enrolled in this study. Tumor specimens underwent immunohistochemical staining for PD-L1, PD-L2, GLUT1, HIF-1 alpha, VEGFR2, VEGF-C, and beta 2 adrenergic receptor. Results: High uptakes of SUVmax, SUVmean, MTV, and TLG were identified in 28 (25.9%), 61 (56.5%), 55 (50.9%), and 55 (50.9%) of 108 patients, respectively. High uptake of SUVmax significantly correlated with PS (performance status) of 1-2, thymic carcinoma, and advanced stage, and SUVmax on F-18-FDG uptake displayed a close association with PD-L1 and PD-L2 expressions, but not with MTV and TLG. Our analysis revealed that SUVmax was identified as being significant relationship for positive PD-L1/PD-L2 expression. GLUT1, HIF-1 alpha, and VEGFR2 were significantly associated with the expression of PD-L1/PD-L2 from the biological viewpoint. Conclusion: F-18-FDG accumulation was closely associated with the expression of PD-L1/PD-L2, which, in turn, was correlated with glucose metabolism and hypoxia. PD-L1/PD-L2 could affect the glucose metabolism and hypoxia in thymic tumor cells.