DIPG-56. EXPLORATION OF TUMOR/STROMA INTERACTIONS IN DIPG XENOGRAFT BY SPECIES-SPECIFIC RNA-SEQ DECONVOLUTION INDICATES A ROLE OF MICROGLIA CELL IN DIPG DEVELOPMENT

Abstract

Diffuse Intrinsic Pontine Glioma (DIPG) and more largely Diffuse Midline Gliomas H3 K27M-mutant (DMG) harbor a unique property of infiltration. Our objective is to elucidate/describe the cellular and molecular determinants of micro-environmental modifications resulting from the tumour/stroma dialogue as it might provide pro-invasive conditions that favour the development of the disease. To this end, we performed RNA-seq analyses to characterize exhaustively the bidirectional molecular modifications of the stroma/tumour in DIPG xenograft models. Gene expression changes in murine microenvironment compartment were investigated as continuous or semi-continuous traits of tumor load by measuring transcriptome in zone with high vs. low infiltration. We observed substantial modulations in gene expression in the microenvironment associated with increasing tumor cell content, pointing to a modification of the macrophage/microglial infiltrate. The expression or overexpression of several modulated genes was validated by IHC in the stroma of DMG primary tumors. Among them, overexpression of the cytokine CCL3 was confirmed, reflecting the activation status of microglial cells. Moreover, we observed in patients that the density of IBA-1 positive microglial cells increases according to the extent of tumor infiltration and that a significant part of them harbor a mitotic status, supporting their interaction with DMG cells. The involvement of this interaction in DMG development needs further evaluation and might represent opportunity to slow down DIPG extension.