Abstract
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.
Highlights
Extranodal NK/T cell lymphoma (ENKTL), nasal type, is a rare type of lymphoma that ordinarily involves midline areas of the nasal cavity, oral cavity, and adjacent s ites[1]
Two cases of immune evasion A (IE-A), two cases of immune evasion B (IE-B), and a case of immune silenced (IS) in which tumor immune microenvironment (TIME) subtype was confirmed at relapse were included for analysis
Progressive necrotic lesions, located mainly in the nasal cavity, are a major clinical feature of extranodal NK/T cell lymphoma (ENKTL) that is associated with miserable prognosis and distant m etastases[17,18]
Summary
Extranodal NK/T cell lymphoma (ENKTL), nasal type, is a rare type of lymphoma that ordinarily involves midline areas of the nasal cavity, oral cavity, and adjacent s ites[1]. The IS group, classified by low FoxP3 and PD-L1 without high CD68 (a unique morphologic change in CD68 and macrophages), displayed an exhausted immune response. Patients in this group mainly showed advanced stages and were resistant to immune checkpoint inhibitors, such as pembrolizumab and n ivolumab[4]. Several studies describe the complex interactions between the immune environment and cancer cells and their influence on tumor development and metastasis[11,12] It remains unknown how FDG uptake pattern might be associated with the state of the immune environment surrounding ENKTLs according to histologic and clinical data. The study was organized to determine whether IS subtype, which has poor response to immunotherapies, might be distinguished by FDG PET/CT
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
