IM-06 * A BIOINFORMATICS EVALUATION OF TUMOR-ASSOCIATED MACROPHAGES ACROSS 2 BRAIN TUMOR TYPES

Abstract

BACKGROUND: CD163, the membrane form of a M2 macrophage marker, is exclusively expressed on alternatively activated or M2 macrophages. In some tumors such as neuroblastoma, CD163+ tumor-associated macrophages (TAMs) were shown to correlate with metastatic disease, age and outcome. Recently, the presence of TAMs has been demonstrated in some brain tumors, with evidence of origins from monocyte-derived macrophages fromperipheral blood, and not brain resident microglial. AIM: (1) To evaluate CD163 expression using gene expression data, in 2 brain tumor types, medulloblastoma (MB) and glioblastoma multiforme (GBM); (2) To correlate CD163 expression with prognostic outcome in MBs and GBMs. METHODS: We analyzed CD163 gene expression in MBs (n = 60, Affymetrix U133 plus 2.0 platform) from Texas Children's Cancer Center and GBMs from TCGA dataset (n = 168, RNA sequencing). RESULTS: Previously, we provided evidence that the quantitative expression of CD163, indicative of CD163+TAMs infiltration, was distinct among molecular subtypes of MBs, Sonic-Hedgehog-activated tumors were the most enriched (p = 0.006). We further discovered that CD163 expression was also distinct among molecular subtypes of GBMs, with Mesenchymal subtype being most enriched (p = 0.0006). CONCLUSIONS: These findings highlight the therapeutic implications on the pathogenesis role and therapeutic targeting aspects of CD163+ macrophages in different molecular subtypes of 2 brain tumor types. M2 macrophages serve a greater regulatory function than effector killing function associated with classically activated macrophages. IL10 secreted byM2macrophages are also implicated in angiogenesis necessary for tumor growth and proliferation. In addition, TAMs cross-present tumor-derived endogenous ligands and can be specifically recognized and killed by natural-killer-T-cells.