TMIC-37. AN ADVANCED PHAGOCYTOSIS GLIOMA THERAPY BASED ON MICROGLIA: INSIGHT FROM AD THERAPY

Abstract

Abstract INTRODUCTION Alzheimer's disease (AD) has an inverse correlation with glioma incidence. AD brain present a suppressive environment for glioma initiation and progression caused by amyloid β42 (Aβ42) activation of microglia. However, the underlying mechanisms remain elusive. METHODS Public database of patients with AD and brain cancer were collected and analyzed for the correlation between the two distinct diseases. The level of Aβ42 expression was examined by IHC staining in lower-grade glioma (LGG) and higher-grade glioma (HGG). Glioma-bearing mice were applied to evaluate the tumor suppressive effect induced by oligomer Aβ42 (OAβ42) in vivo. The co-culture system was applied to study the mechanism of OAβ42 activated microglia and enhanced tumor cell phagocytosis. RNA sequencing was performed to identify the underlying molecular mechanism involved in OAβ42 potentiated microglial phagocytosis. RESULTS OAβ42 is an innate peptide and a favorable prognostic biomarker of glioma with a prolonged OS in LGG than HGG (P=0.04). Injection of OAβ42 could inhibit the growth of glioma (P=0.0003) through enhancing microglial phagocytosis in the allogeneic mouse model. And the overall survival of the OAβ42 treated mice was longer than the vehicle group (P=.037). The OAβ42 primed microglia phagocytized more glioma cells than vehicle control in a co-culture system (P=0.0007). Autocrine of insulin-like growth factor 1(IGF-1) from OAβ42 activated microglia is essential for engulfing tumor cells. CONCLUSIONS Our findings proved OAβ42 modulated microglia could serve as a cellular target for treatment of glioma. Furthermore, our study provides a novel conceptual therapeutic strategy through modulating the function of existing immune cells in the microenvironment.