IMST-55. LYMPH NODE AND URINE METABOLOMICS: A NON-INVASIVE STRATEGY TO PREDICT EFFICACY OF DENDRITIC CELL VACCINE IMMUNOTHERAPY

Abstract

We recently demonstrated that robust migration of DCs to the draining lymph nodes was essential for survival benefit in GBM patients receiving DC vaccines. In this study we evaluated the early phase of immune-activation in lymph nodes and the subsequent metabolic changes in the urine to predict the outcome of DC based immunotherapy. DCs were generated from the bone marrow of adult mice. DCs were harvested, electroporated with OVA mRNA and used to vaccinate mice that received OT-1 splenocytes. After vaccination, the animals underwent lymph node and bladder magnetic resonance imaging (MRI) spectroscopy and had collection of urine and draining lymph nodes for nuclear magnetic resonance (NMR) spectroscopy analysis and flow cytometry. Lymphocytes from vaccinated animals demonstrated an increase in alpha ketoglutarate and lactate by flow cytometry. A more in depth metabolic analysis was performed of these cells using NMR spectroscopy that demonstrated an overall increase in all metabolic spectral signals correlating with an increase in lymphocytes in vaccinated lymph nodes. MRI spectroscopy demonstrated changes in fat signals in the vaccinated lymph nodes compared to control lymph nodes but no significant metabolic differences. In contrast, the bladder of DC vaccinated animals showed unique MRI spectral signatures that were not observed in control animals including increases in urea, taurine, creatinine, and citrate. Furthermore, specific signals were detected in urine NMR spectra of the DC vaccinated animals that were absent in control animals. Urine NMR and MRI spectroscopy are feasible and demonstrate metabolic changes induced by vaccine initiated immune response. Further experiments are needed to establish these findings as biomarkers for vaccine functionality.