Increased infiltration of CD8 T cells in recurrent glioblastoma patients is a useful biomarker for assessing the response to combined bevacizumab and lomustine therapy.

PURPOSE:Treatment options for recurrent glioblastoma (rGBM) remain scarce, which may be due to the limited understanding of its molecular characteristics. METHODS:Based on gene expression profiling, the infiltration scores of 26 immune cell types were calculated using gene set variation analysis. The differences between rGBM and other cancer subtypes were estimated to characterize the specific immune characteristics of rGBM, and the prognostic value of immune cells in rGBM was estimated using univariate and multivariate Cox analysis. Subgroup analyses and Kaplan-Meier analyses were performed to identify whether CD8 T-cell infiltration could be useful in selecting treatment options for rGBM patients. RESULTS:We found that rGBM patients were associated with enrichment of activated CD8 T cells, and high CD8 T-cell infiltration was associated with superior overall survival. Patients exhibiting high CD8 T-cell infiltration who received treatment with bevacizumab and lomustine combination therapy experienced a significant benefit in overall survival and progression-free survival, whereas patients with low CD8 T-cell infiltration did not experience such a benefit. CD8 T cells remained an independent prognostic factor in multivariate analyses (cohort 1: hazard ratio [HR] = 0.546, 95% confidence interval [CI]: 0.316-0.945, P = 0.031; cohort 3: HR = 0.615, 95% CI: 0.387-0.978, P = 0.040) after adjusting for clinicopathological and molecular factors. CONCLUSIONS:Activated CD8 T-cells is a promising biomarker for predicting overall survival in rGBM patients and could be used for assisting treatment selection.