Tumor-associated macrophages (TAMs) can directly clear tumor cells and enhance the phagocytic ability of immune cells. An abundance of TAMs at the site of the glioblastoma tumor indicates that TAM-targeting immunotherapy could represent a potential form of treatment for this aggressive cancer. Herein, we discuss: i) the dynamic role of TAMs in glioblastoma; ii) describe the formation of the immunosuppressive tumor microenvironment; iii) summarize the latest clinical trial data that reveal how TAM function can be regulated in favor tumor eradication; and lastly, iv) evaluate the implications of existing and novel translational approaches for treating glioblastoma in clinical practice.

Background Solute carrier family 25 member 32 (SLC25A32) is an important member of SLC25A family and plays a role in folate transport metabolism. However, the mechanism and function of SLC25A32 in the progression of human glioblastoma (GBM) remain unclear. Methods In this study, folate related gene analysis was performed to explore gene expression profiles in low-grade glioma (LGG) and GBM. Western blotting, real-time quantitative PCR (qRT-PCR), and immunohistochemistry (IHC) were used to confirm the expression levels of SLC25A32 in GBM tissues and cell lines. CCK-8 assays, colony formation assays, and Edu assays were performed to assess the role of SLC25A32 on proliferation in GBM in vitro. A 3D sphere invasion assay and an ex vivo co-culture invasion model were performed to assess the effects of SLC25A32 on invasion in GBM. Results Elevated expression of SLC25A32 was observed in GBM, and high SLC25A32 expression was associated with a high glioma grade and poorer prognosis. Immunohistochemistry performed with anti-SLC25A32 on samples from an independent cohort of patients confirmed these results. Knockdown of SLC25A32 inhibited the proliferation and invasion of GBM cells, but overexpression of SLC25A32 significantly promoted cell growth and invasion. These effects were mainly due to the activation of the PI3K-AKT-mTOR signaling pathway. Conclusion Our study demonstrated that SLC25A32 plays a significant role in promoting the malignant phenotype of GBM. Therefore, SLC25A32 can be used as an independent prognostic factor in patients with GBM, providing a new target for the comprehensive treatment of GBM.

A strategy combining biomimetic nanomaterial scaffolds with neural stem cell (NSC) transplantation holds promise for spinal cord injury (SCI) treatment. In this study, innovative three-dimensional (3D) nanofibrous sponges (NSs) are designed and developed by a combination of directional electrospinning and subsequent gas-foaming treatment. The as-generated 3D NSs exhibit uniaxially aligned nano-architecture and highly controllable hierarchical structure with high porosity, outstanding hydrophilicity, and reasonable mechanical performance, and they are demonstrated to facilitate cell infiltration, induce cell alignment, promote neuronal differentiation of NSCs, and enhance their maturation by activating the cellular adhesion molecule (CAM) pathways. The in vivo data show that the NSC-seeded 3D NSs efficiently promote axon reinnervation and remyelination in a rat SCI model, with new “neural relays” constructed across the lesion gap. Notably, they significantly increase the neurological motor scores of SCI rats from ~2 to 16 (out of 21) and decrease the sensing time from 140 s to 36 s, accompanied by the restoration of ascending and descending electrophysiological signalling. Overall, the present study indicates that the as-fabricated 3D NSs can effectively regulate the fate of NSCs, and an advanced combination of 3D NS design and transplanted NSCs invites applications as an ideal tissue-engineered scaffold for SCI repair.