Abstract 7448: Serum IL-10 is associated with neurologic symptoms and interference in primary brain tumor patients
Authors: Kaitlynn A. Slattery, Michelle L. Wright, Dhaivat Raval, Emory Hsieh, McKenzie C. Kauss, Terri S. Armstrong, Tito R. Mendoza, Vivian A. Guedes
Journal: Cancer Research (2024)

Abstract Background: Primary brain tumors (PBT) are associated with neurocognitive symptoms as a direct result of the tumor or its treatment. IDH-mutant gliomas are associated with longer survival, but with higher incidence of seizures and neurocognitive symptoms.​ Correlations between cytokines and neuroinflammation have been reported in other structural brain lesions but have not been evaluated in PBT. Here, we investigate elevated peripheral blood levels of proteins (cytokine levels) in a cross-sectional cohort (n=47) of adult, IDH-mutant PBT patients enrolled in a natural history study (NCT02851706, PI: T. Armstrong) versus healthy subjects (n=32) and the correlations between cytokine levels and patient-reported outcomes (PROs). Methods: Patient-reported symptoms and activity-related interference were collected via the MD Anderson Symptom Inventory-Brain Tumor at study entry. Serum samples were stored at -80°C for batch processing and used for biomarker analysis. Ten cytokines (interleukin-1β [IL-1β], IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon-γ [IFN-γ], and tumor necrosis factor-α [TNF-α]) were quantified in duplicate using an immunoassay (V-Plex/Proinflammatory, Meso Scale Discovery [MSD], Rockville, MD). Lab personnel were blinded to diagnosis and patient clinical status. Mean concentration (pg/mL) levels or ‘present or not detectable’ values were used. Descriptive statistics, Mann-Whitney tests, and Spearman correlations were conducted at p &amp;lt;0.05. Results: The patient sample was mostly male (62%), White (70%), employed (64%), had no prior recurrence (62%), high grade (3-4) tumors (70%), and an average age at diagnosis of 36 years (SD: 9; median: 34; range: 20-53). The healthy subject sample was mostly female (53%) and White (72%), with an average age of 46 years (SD: 19; median: 50; range: 19-78). Five cytokines (IFN-γ, IL-6, IL-8, IL-10, and TNF-α) were detectable in patients and healthy subjects with levels of IL-6, IL-10, and TNF-α higher in patients than healthy subjects. Serum levels of IL-10 (mean rank=50.7 vs 24.3, p&amp;lt;0.001) and TNF-α (mean rank=50.6 vs 24.2, p&amp;lt;0.001) were higher in PBT patients when compared to healthy subjects. Only IL-10, but not other cytokines, positively correlated with severity of patient-reported symptoms [pain (r=0.290, p=0.048), numbness/tingling (r=0.302, p=0.039)], and activity-related interference, including work (r=0.323, p=0.027), and walking (r=0.402, p=0.005). Conclusions: Higher IL-10 levels and detection differences in other cytokines, may indicate a reduction in immune-mediating processes and heightening inflammation in patients. Future analysis will include replication of this work in a larger cohort across PBT types to evaluate risk, explore mechanisms, and associations with treatment types. Citation Format: Kaitlynn A. Slattery, Michelle L. Wright, Dhaivat Raval, Emory Hsieh, McKenzie C. Kauss, Terri S. Armstrong, Tito R. Mendoza, Vivian A. Guedes. Serum IL-10 is associated with neurologic symptoms and interference in primary brain tumor patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7448.