Chemokine expression profile of freshly isolated human glioblastoma-associated macrophages/microglia.

Several studies have substantiated the hypothesis that tumor progression is not only driven by the tumor cells themselves but also by their interaction with intrinsic and surrounding stromal cells. Tumor-associated macrophages and microglial cells (TAMs) represent one major stromal cell component of glioblastomas. Additionally, in many gliomas, chemokines are highly expressed and some chemokines were already linked to settlement of TAMs in tumors. However, although chemoattraction mechanisms mediated by chemokines and their receptors are well documented, information on their expression and role in TAMs, particularly in patients, is limited. Therefore, we investigated the transcription of the chemokine-receptor combinations CXCL12-CXCR4-CXCR7, CXCL16-CXCR6 and CX3CL1-CX3CR1 in freshly isolated TAMs from 20 human glioblastomas in relation to in vitro polarized M1- and M2-macrophages. We demonstrated that TAMs express both M1- and M2-markers. Compared to in vitro polarized macrophages, the M1-marker interleukin (IL)-6 was similarly expressed, whereas IL-1β and tumor necrosis factor (TNF)-α were found at lower levels. The M2-marker IL-10 was comparably expressed, while CD163 and transforming growth factor (TGF)-β were detected with one tenth lower intensities in TAMs. All investigated chemokines/receptors were transcribed at moderate to high levels in TAMs as well as in vitro polarized macrophages. However, CX3CR1 was markedly higher and CXCR7 was somewhat higher expressed in TAMs, whereas M2-macrophages were characterized by the highest CXCL12 and a moderate CX3CL1 expression. Collectively, TAMs share properties of M1- and M2-macrophages and show a considerably higher expression of the chemokine receptors CXCR7 and CX3CR1.