IMMU-18. MIGRATION OF DENDRITIC CELLS THROUGH THE BRAIN-MENINGEAL LYMPHATIC-DRAINING LYMPH NODE NETWORK IN ORTHOTOPIC GLIOMA MODELS

Abstract INTRODUCTION Limited migration of dendritic cell (DC) vaccines to draining lymph nodes (DLN) remains a major limitation DC efficacy for malignant gliomas. Our prior work demonstrated that increased peripheral DLN results in enhanced antitumor efficacy. Given this, we studied trafficking mouse gliomas, the meningeal lymphatic vessel (MLV) system, and cervical (CLN). METHODS To elevate host populations, C57BL/6 VMDk mice were implanted with B16-FMS-like tyrosine kinase 3 ligand (FLT3L) melanoma or B16-FLT3L supernatant. Mice intracranially CT2A, GL261-OVA, SMA560 syngeneic glioma lines right parietal lobe. Antitumor was measured by tumor weights median overall survival (mOS). RESULTS injected into hemispheres display delayed kinetics peak CLN compared control (7 days (d) vs 3d post-injection (pi), respectively). Migration intraventricular (ivn)-injected is superior at 1, 7 pi when present (p = 0.026). supernatant disproportionate systemic expansion conventional type 1 over 2 (cDC1 > cDC2) media (cDC1, cDC2 fold change spleen 27,11; 6,2; blood 6,3). Pulsed dosing FLT3L significantly greater numbers splenic cDC1 daily 0.002). CT2A continuous secretion vivo show longer (mOS 30d) GM-CSF 22d) 0.009). have reduced growth alone, GM-CSF-secreting tumors, mixed FLT3L/GM-CSF-secreting tumors 0.029). CONCLUSION signaling generation through CNS more favorable Modeling glioma-MLV-CLN system stimulation permits testing strategies improve therapy.