Os13.6.a survival is associated with circulating b-cells and age among oligodendroglioma patients

Abstract BACKGROUND Though patients with oligodendroglioma have improved outcomes versus astrocytomas, there remains marked variability in their survival experience that is unexplained by known prognostic factors. Immunomethylomics uses DNA methylation as a substitute for flow cytometry to characterize immune cells in whole blood. We applied immunomethylomics to archived samples from patients with oligodendroglioma enrolled in the UCSF Adult Glioma Study (AGS) to assess the impact of immune-related characteristics on prognosis. MATERIAL AND METHODS We used immunomethylomics to evaluate immune cell fractions in archived whole blood from the AGS. We identified 141 patients with oligodendroglioma (IDH and TERT mutant, and 1p19q co-deleted) and compared them to other adult diffuse glioma subtypes (N = 347) and controls (N = 454). RESULTS The median age at diagnosis of the 141 oligodendrogliomas was 44 years (range 19 - 83), 57% were male, and 75% white. A total of 60% of patients had received chemotherapy, with or without radiation, prior to blood draw and 25% were taking dexamethasone at the time of sample collection. Oligodendroglioma patients had lower proportions of B cell fractions (total, memory, naïve) than people without glioma. Still, there were higher proportions of B cell (total, memory) and lymphocyte fractions (total, CD4-total and memory), basophil, eosinophil, and NK cells in oligodendrogliomas compared to other glioma subtypes. Median overall survival for the oligodendrogliomas was 17.5 years (95% CI 16.9 - NA) with median follow-up time of 12 years (95% CI 11 - 14). Recursive partitioning analysis delineated two statistically significantly different survival groups for oligodendroglioma patients based on an interaction between age at diagnosis and B naïve cell proportions. The group with the best outcome had a median survival of 24.2 years (95% CI 20.4 - NR) comprised of patients </= 42 years of age with a higher proportion of B naïve cells (>1.91%) (N = 37). The group with the worse outcome had a median survival of 16.9 years (14.8 - NR) and included patients </= 42 years of age with a lower proportion of B naïve cells (</= 1.91%) (N = 28) OR patients > 42 years of age (N = 76) (p = 0.00032). Additionally, proportions of lymphocyte fractions (CD4 and CD8 total, memory, and naïve) were significantly lower in the worse outcome group. Grade or prior treatment did not differ between the groups. CONCLUSION We identified an interaction between age and B naïve cell proportions that distinguished survival outcomes for patients with oligodendrogliomas. Immunomethylomics is a powerful tool for assessing immune status and these findings suggest that blood-immune characteristics may play a vital role in the prognosis of patients with gliomas.