OP27FEASIBILITY OF USING CIRCULATING DENDRITIC CELLS IN CANCER VACCINE TREATMENTS FOR GLIOBLASTOMA

Abstract

INTRODUCTION: Glioblastoma (GBM) progression occurs through immune evasion. Furthermore the immunosuppressive drug, dexamethasone (DEX) ameliorates symptoms with unknown effects on the tumour microenvironment. Here we present novel data on GBM patients' four circulating dendritic cells types (DCs) - myeloid type 1 (MDC1) and type 2 (MDC2), slan- (SLAN) and plasmacytoid (pDC), vital for tumour immune detection and orchestrating the cytotoxic response. Furthermore we isolate MDC1 and assess function on exposure to GBM lysate, DEX and manipulation through the mitogen activated protein kinase, p38. METHOD: (1) 9-parameter whole-blood flow cytometry was used to measure the abundance of circulating DC of both GBM patients and age matched healthy controls. Patients were unselected to represent the clinical breadth of disease status and standard therapies. (2) MDC1 were isolated from peripheral blood by magnetic bead selection of CD1c+ cells (n = 6) and exposed to tumour lysate (U87), DEX and, p38 inhibitor (p38i) prior to stimulation. MDC1 cytokine secretion was measured by ELISA for IL-12 and IL-10. RESULTS: (1) Circulating MDC1, MDC2 and SLAN DCs although showing a trend of reduction, only pDC were significantly supressed in patients (n = 13) compared to age matched healthy controls (n = 14). (2) MDC1s exposed to tumour lysate and/or DEX ablated IL-12 secretion and increased IL-10, representing an immunosuppressive environment. This could be partially reversed by the addition of p38i. CONCLUSION: MDC1 are available in sufficient numbers to consider novel adoptive transfer in cancer vaccines. The addition of p38i polarised cytokine profile to a favourable T cell cytotoxic response, highlighting its potential as a vaccine adjunct.