Metabolic activity of extranodal NK/T cell lymphoma on ¹⁸F-FDG PET/CT according to immune subtyping

Disseminated extranodal NK/T cell lymphoma (ENKTL) is associated with dismal prognosis. Hence, distinct tumor immune microenvironment (TIME) subtypes were proposed to explain their influence on ENKTL progression and help predict treatment response. In this study, we investigated the capacity of FDG PET/CT to discern ENKTL TIME subtypes. A total of 108 pretreatment FDG PET/CT scans of 103 patients with newly diagnosed or relapsed ENKTL were retrospectively analyzed. TIME subtype was determined using three key immunohistochemical markers. SUVmax, MTV and TLG were measured, and metabolic features associated with TIME subtype were statistically extracted. TIME subtype was immune tolerance (IT) in 13.9%, immune evasion A (IE-A) in 56.5%, immune evasion B (IE-B) in 21.3%, and immune silenced (IS) in 8%. The IS group showed the highest SUVmax (15.9 ± 6.4, P = 0.037), followed by IE-A (14.1 ± 7.8), IE-B (10.9 ± 5.6), and IT groups (9.6 ± 5.1). Among 53 with only nasal FDG lesions, 52 had non-IS subtype. Among 55 with extra-nasal FDG lesions, those with IS subtype more often had adrenal (P = 0.001) or testis involvement (P = 0.043), greater MTV (P = 0.005), greater TLG (P = 0.005), and SUVmax located at extra-nasal sites. The presence of 0–2 and 3–4 of these four findings was associated with low probability (2/46) and high probability (6/9) of IS subtype, respectively. Furthermore, patients showing IS subtype-favoring PET/CT pattern had worse overall survival compared to their counterparts. These results demonstrate that FDG PET/CT can help predict immune subtype in ENKTL patients. The different patterns between glycolytic activity and involved site according to TIME subtype might be related to the interplay between tumor cells and immune cells in the tumor microenvironment.