Glioblastoma multiforme (GBM) is the most malignant intracranial tumor in adults, characterized by extensive infiltrative growth, high vascularization, and resistance to multiple therapeutic approaches. Among the many factors affecting the therapeutic effect, the immunosuppressive GBM microenvironment that is created by cells and associated molecules via complex mechanisms plays a particularly important role in facilitating evasion of the tumor from the immune response. Accumulating evidence is also revealing a close association of the gut microbiota with the challenges in the treatment of GBM. The gut microbiota establishes a connection with the central nervous system through bidirectional signals of the gut–brain axis, thus affecting the occurrence and development of GBM. In this review, we discuss the key immunosuppressive components in the tumor microenvironment, along with the regulatory mechanism of the gut microbiota involved in immunity and metabolism in the GBM microenvironment. Lastly, we concentrate on the immunotherapeutic strategies currently under investigation, which hold promise to overcome the hurdles of the immunosuppressive tumor microenvironment and improve the therapeutic outcome for patients with GBM.

Because of the short read length of high throughput sequencing data, assembly errors are introduced in genome assembly, which may have adverse impact to the downstream data analysis. Several tools have been developed to eliminate these errors by either 1) comparing the assembled sequences with some similar reference genome, or 2) analyzing paired-end reads aligned to the assembled sequences and determining inconsistent features alone mis-assembled sequences. However, the former approach cannot distinguish real structural variations between the target genome and the reference genome while the latter approach could have many false positive detections (correctly assembled sequence being considered as mis-assembled sequence). We present misFinder, a tool that aims to identify the assembly errors with high accuracy in an unbiased way and correct these errors at their mis-assembled positions to improve the assembly accuracy for downstream analysis. It combines the information of reference (or close related reference) genome and aligned paired-end reads to the assembled sequence. Assembly errors and correct assemblies corresponding to structural variations can be detected by comparing the genome reference and assembled sequence. Different types of assembly errors can then be distinguished from the mis-assembled sequence by analyzing the aligned paired-end reads using multiple features derived from coverage and consistence of insert distance to obtain high confident error calls. We tested the performance of misFinder on both simulated and real paired-end reads data, and misFinder gave accurate error calls with only very few miscalls. And, we further compared misFinder with QUAST and REAPR. misFinder outperformed QUAST and REAPR by 1) identified more true positive mis-assemblies with very few false positives and false negatives, and 2) distinguished the correct assemblies corresponding to structural variations from mis-assembled sequence. misFinder can be freely downloaded from https://github.com/hitbio/misFinder .

5-Demethylnobiletin is the active ingredient in citrus polymethoxyflavones that could inhibit the proliferation of several tumor cells. However, the anti-tumor effect of 5-Demethylnobiletin on glioblastoma and the underlying molecular mechanisms are remains unknown. In our study, 5-Demethylnobiletin markedly inhibited the viability, migration and invasion of glioblastoma U87-MG, A172 and U251 cells. Further research revealed that 5-Demethylnobiletin induces cell cycle arrest at the G0/G1 phase in glioblastoma cells by downregulating Cyclin D1 and CDK6 expression levels. Furthermore, 5-Demethylnobiletin significantly induced glioblastoma cells apoptosis by upregulating the protein levels of Bax and downregulating the protein level of Bcl-2, subsequently increasing the expression of cleaved caspase-3 and cleaved caspase-9. Mechanically, 5-Demethylnobiletin trigged G0/G1 phase arrest and apoptosis by inhibiting the ERK1/2, AKT and STAT3 signaling pathway. Furthermore, 5-Demethylnobiletin inhibition of U87-MG cell growth was reproducible in vivo model. Therefore, 5-Demethylnobiletin is a promising bioactive agent that might be used as glioblastoma treatment drug.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor with a median survival of less than one year. EGFR and EGFRvIII amplification are significant genetic signature in GBM. Currently, the treatment targeting EGFRvIII cannot effectively prolong the survival of patients. TGF-β is secreted by a variety of cells in the GBM immunosuppressive microenvironment, mediating the malignant progression of EGFRvIII-expressing GBMs, but the precise mechanism is still unclear. Our data demonstrated that IGFBP3 is produced by TGF-β and EGFRvIII signal transactivation. The transcription factor c-Jun activation is essential for the production of IGFBP3. IGFBP3 knockdown not only decreased the activation of TGF-β and EGFRvIII signaling pathways, but also reduced the malignant behaviors of EGFRvIII-expressing GBM cells. In vivo data also showed that IGFBP3 knockdown prolonged tumor growth and reduced tumor volume in xenograft models. Through analysis of 80 clinical specimens showed that the expression of EGFRvIII and IGFBP3 in GBM tissues was significantly increased and positively correlated. In conclusion, TGF-β regulates the production of IGFBP3 through the EGFRvIII/c-Jun/IGFBP3 signal axis, therefore, IGFBP3 may serve as a promising therapeutics target for EGFRvIII-positive GBMs.