Predictive Biomarkers for the Responsiveness of Recurrent Glioblastomas to Activated Killer Cell Immunotherapy

Glioblastoma multiforme (GBM) is the most common and aggressive primary malignant brain tumor, but the current therapeutic approaches have very limited impact on increase of the patients’s survival with GBM. Our recent clinical trial with autologous activated nature killer (NK) cells (AKCs) including 14 patients with recurrent GBM found that the progression-free and overall survival times were significantly increased in some patients in the treatment group. In the present study, we identified TNFRSF18, TNFSF4, and IL12RB2 as biomarkers that predict response to NK cell therapeutics by studying the tumor-immune microenvironment using NanoString and qRT-PCR analyses. In addition, our results show that responders to NK therapy have an immune-activated tumor microenvironment, whereas non-responders do not. Considering that immune and inflammatory response-enrichment is related to the high-risk group in this tumor type, our findings highlight a new treatment strategy of NK cell therapeutics for patients with highly aggressive recurrent GBM. The mRNA expression of recurred GBM patinets before autologous activated natural killer cell immunotherapy were measured by NanoString nCounter PanCancer Immune Profiling panel.