Gene Expression Profile Correlates with T-Cell Infiltration and Relative Survival in Glioblastoma Patients Vaccinated with Dendritic Cell Immunotherapy

摘要: Purpose: To assess the feasibility, safety, and toxicity of autologous tumor lysate–pulsed dendritic cell (DC) vaccination toll-like receptor (TLR) agonists in patients with newly diagnosed recurrent glioblastoma. Clinical immune responses were monitored correlated gene expression profiles. Experimental Design: Twenty-three glioblastoma (WHO grade IV) enrolled this dose-escalation study received three biweekly injections glioma lysate-pulsed DCs followed by booster vaccinations either imiquimod or poly-ICLC adjuvant every 3 months until progression. Gene profiling, immunohistochemistry, FACS, cytokine bead arrays performed on patient tumors peripheral blood mononuclear cells. Results: DC are safe not associated any dose-limiting toxicity. The median overall survival from time initial surgical diagnosis was 31.4 months, a 1-, 2-, 3year rate 91%, 55%, 47%, respectively. Patients whose had mesenchymal signatures exhibited increased following compared historic controls same genetic subtype. Tumor samples signature higher number CD3 þ CD8 tumor-infiltrating lymphocytes glioblastomas other (P ¼ 0.006). Conclusion: Autologous conjunction TLR is as therapy patients. Our results suggest that profile may identify an immunogenic subgroup be more responsive to immune-based therapies. Clin Cancer Res; 17(6); 1603–15. � 2010 AACR.