The Unique Metabolomics Based Biomarkers Of Response To Immunotherapy For Glioblastoma

Abstract INTRODUCTION The adaptive immune response requires robust T cell proliferation and activation. These T cell changes are dependent on metabolic program shifts that can be measured using metabolomic analysis. The objective of this project was to identify a metabolomics profile to serve as a biomarker of response to immunotherapy for the treatment of brain tumors. METHODS GL261-gp100 tumor-bearing mice were received anti-PD1 or bone marrow-derived dendritic cell (DC) vaccine that was generated ex vivo. Urine samples were collected for Nuclear Magnetic Resonance (NMR) analysis. A more in-depth Sparse Partial Least Squares Discriminant Analysis (sPLS-DA) revealed global metabolic changes induced with immunotherapy. RESULTS The metabolic changes were most dramatic at 24 hours post DC vaccination and slowly returned to baseline at 7 days post DC vaccination. The main drivers of the differences included creatine, n-dimethyl glycine, alanine, lactate, glucose, glutamine, leucine, citrate and formate. Anti-PD1 therapy-related metabolic changes were largest around day 20 post therapy and the main drivers of the differences included dimethyl sulfone, succinate, lactate and isobutyrate. CONCLUSION Immunotherapy results in systemic metabolic changes that serve as a biomarker treatment effect. These findings have translational relevance in predicting patients who will develop an immune response to immunotherapy and ultimately have better outcomes with treatment.