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

2-deoxy-2-[fluorine-18] fluoro-d-glucose (¹⁸ F-FDG) positron emission tomography (¹⁸ F-FDG-PET) is a convenient modality to assess the metabolic activity within tumor cells. However, there is no consensus regarding the relationship between ¹⁸ F-FDG uptake and the immune environment in thymic epithelial tumors (TETs). We conducted a clinicopathological study to elucidate the relationship between ¹⁸ F-FDG uptake and programmed death ligands 1 and 2 (PD-L1/PD-L2) expression in patients with TETs.

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 ¹⁸ F-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-1α, VEGFR2, VEGF-C, and β2 adrenergic receptor.

High uptakes of SUV_max , SUV_mean , 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 SUV_max significantly correlated with PS (performance status) of 1-2, thymic carcinoma, and advanced stage, and SUV_max on ¹⁸ F-FDG uptake displayed a close association with PD-L1 and PD-L2 expressions, but not with MTV and TLG. Our analysis revealed that SUV_max was identified as being significant relationship for positive PD-L1/PD-L2 expression. GLUT1, HIF-1α, and VEGFR2 were significantly associated with the expression of PD-L1/PD-L2 from the biological viewpoint.

¹⁸ F-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.