Abstract
Glioblastoma (GBM) is one of the most aggressive primary brain tumors in adults. Despite various strategies, including differential single-cell gene expression analyses between GBM and healthy tissues, none of the resulting findings could benefit the development of promising therapies, yet. Various macrophage populations coevolve in the tumor microenvironment of GBMs and not only support tumor immune evasion but also tumor spreading throughout the surrounding tissue. To distillate unique immune cell features of GBMs, we compared their immune cell composition with other central nervous system (CNS) tumor entities, in particular meningiomas (MNGs), non-GBM gliomas, and metastases (MTS). We could identify a macrophage population characterized by the coexpression of CX3CR1 and Siglec10, representing a potential indicator population of GBMs. This GBM-specific macrophage subset might be supported by a glioma-characteristic lipid mediator (LM) milieu of enriched docosahexaenoic acid (DHA) and its lipoxygenase (LOX)-derived metabolites. Moreover, the GBM tumor microenvironment (TME) is enriched in arachidonic acid (AA)-derived cyclooxygenase (COX) products prostaglandins (PG) E(2) and F(2α) in combination with enhanced CD24 expression. By our comparative approach, the data hint toward a pro-tumorigenic Siglec10(+)CX3CR1(+) macrophage population depending on the characteristic tumor microenvironment (TME) of highly malignant GBMs.