Interactions of Age and Blood Immune Factors and Non-Invasive Prediction of Glioma Survival.

Background Tumor-based classification of human glioma portends patient prognosis; however, considerable unexplained survival variability remains. Host factors (eg, age) also strongly influence survival times, partly reflecting a compromised immune system. How blood epigenetic measures of immune characteristics and age augment molecular classifications in glioma survival has not been investigated. We assess the prognostic impact of immune-cell fractions and epigenetic age in archived blood across glioma molecular subtypes for the first time. Methods We evaluated immune-cell fractions and epigenetic age in archived blood from the University of California San Francisco Adult Glioma Study, including a training set of 197 IDH-wildtype, 1p19q intact, TERT wildtype (IDH/1p19q/TERT-WT) glioma patients, an evaluation set of 350 patients with other subtypes of glioma, and 454 subjects without glioma. Results IDH/1p19q/TERT-WT patients had lower lymphocyte fractions (CD4+T, CD8+T, natural killer, and B cells) and higher neutrophil fractions than subjects without glioma. Recursive partitioning analysis delineated four statistically significantly different survival groups for IDH/1p19q/TERT-WT patients based on an interaction between chronological age and two blood immune factors, CD4+T cells, and neutrophils with median overall survival ranging from 0.76 years [95% confidence intervaI = 0.55 to 0.99] for the worst survival group (n = 28) to 9.72 years [95% confidence intervaI = 6.18 to NA] for the best (n = 33). The Recursive partitioning analysis also statistically significantly delineated four risk groups in patients with other glioma subtypes. Conclusion The delineation of different survival groups in the training and evaluation sets based on an interaction between chronological age and blood immune characteristics suggests that common host immune factors among different glioma types may impact survival. The ability of DNA methylation-based markers of immune status to capture diverse, clinically relevant information may facilitate non-invasive personalized patient evaluation in the neuro-oncology clinic.