TAMI-32. CORRELATION BETWEEN RADIOSENSITIVITY INDEX AND M2 MACROPHAGE PROPORTION IN TUMOR MICROENVIRONMENT OF GLIOBLASTOMA

Abstract

Abstract BACKGROUND Tumor-associated macrophages (TAMs) Macrophage are predominant in glioblastoma tumor microenvironment (TME), supporting for neoplastic cell expansion and invasion. We investigated the relationship between radiosensitivity of glioblastoma and M1/M2 macrophage profiles in bulk and single cell RNA sequencing datasets. METHODS We used radiosensitivity index (RSI) gene signature and estimated RSI score based on the ranking of genes by expression level. Two large glioma datasets – The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) – were employed to identify whether RSI is clinically predictive of overall survival following radiation therapy. To analyze the association between M1/M2 macrophages and RSI within spatial context, the Ivy Glioblastoma Atlas Project dataset was investigated and single cell RNA sequencing dataset (GSE84465) was analyzed as well. Macrophages were profiled using a deconvolution algorithm, CIBERSORTx. RESULTS The RSI-high group having radioresistant tumors showed worse overall survival than the RSI-low group in both the TCGA (HR=1.87, 95% CI=1.06-3.29, P=0.031) and the CGGA (HR=1.61, 95% CI=1.04-2.50, P=0.031) glioblastoma population. In the Ivy Glioblastoma Atlas Project dataset, radiosensitive tumor having lower RSI was significantly more found in more vascular region including hyperplastic and microvascular region (coefficient=-0.07, P=0.001), meanwhile, radioresistant tumor was significantly clustered in necrotic region including perinecrotic and pseudopalisading regions (coefficient=0.07, P< 0.001). The proportion of M1/M2 macrophage and RSI score showed an inverse relationship (coefficient=-0.23, P=0.015), indicating that radioresistant glioblastomas are related with TME having more M2 than M1 macrophage. In single cell RNA sequencing dataset composed of immune and tumor cells collected from four patients, mean RSI of neoplastic cells was positively correlated with high proportion of M2 macrophages. CONCLUSION RSI can predict radiation response in terms of overall survival in glioblastoma patients. High proportion of M2 macrophage may play an important role in TME of radioresistant glioblastoma.