High-grade gliomas (HGGs) in pediatric age have the same bad prognosis as those arising in adults. Approximately one-half of HGGs in children occur in the brain stem, most frequently within the pons as diffuse intrinsic pontine glioma or other midline structures. Although they have the same histological appearance of adult malignant gliomas, in recent years, the extensive use of molecular profiling techniques has demonstrated significant molecular differences between the two age groups. These data have led to a major reclassification of pediatric HGG (pHGG) based on molecular subgrouping with significant clinical correlations in terms of age at presentation, anatomical location, and prognosis. The most important molecular groups are: (1) the histone mutations related pHGG, that is, H3.K27-mutated midline and H3.G34-mutated hemispheric pHGG; (2) the rare isocitrate dehydrogenase (IDH)-mutated pHGG occurring mainly in adolescents; and (3) the H3-/IDH wild type, a heterogenous group of pHGG still object of further molecular stratification. Another important group of pHGG is that occurring in patients with cancer predisposition syndromes such as Li-Fraumeni syndrome, constitutional mismatch repair deficiency, and neurofibromatosis-1 (NF1). In this review, the different subgroups of pHGG and their major driver molecular alterations will be discussed.

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Glioblastoma (GBM, WHO Grade IV) is the most aggressive form of primary brain cancer in adults, and as with other cancers, clinical investigations to use immunotherapy as a possible therapeutic option for GBM are underway. One form of immunotherapy is immune checkpoint inhibition that targets the programmed cell death-1 (PD-1) receptor on lymphocytes. While PD-1 receptor inhibitors, such as pembrolizumab, are often tolerable, there can be dose-limiting immune-related adverse effects, which have the potential to result in impaired health-related quality of life. This case report discusses one patient with recurrent GBM who received pembrolizumab and developed refractory drug-induced arthritis.

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Background: Cytoplasmic activation/proliferation-associated protein-1 (caprin-1) is a newly discovered RNA-binding protein and is now recognized as one of the putative oncogenes. This study was performed to reveal its presence in human gliomas and its oncogenic functions in human glioblastoma-derived Denver brain tumor research group 05 (DBTRG-05MG) cells. Materials and Methods: Clinical glioma samples were cumulatively collected for the identification of caprin-1 using immunoblot analysis and immunofluorescence detection. DBTRG cells transfected with caprin-1-specific small interfering RNA (siRNA) were used to verify caprin-1's oncogenic function using a real-time cell analyzer (RTCA) and scratch assay. Results: Seven of eight collected glioma samples were identified as positive for caprin-1 expression. siRNA dose-responsive inhibition of cell proliferation was observed in DBTRG cells with RTCA, and cell migration rate was significantly reduced by siRNA transfection (P < 0.05). Conclusion: The present study identified the higher expression of caprin-1 in human glioblastoma-derived DBTRG cells. Its oncogenic functions, mainly enhanced cell proliferation and promoted cell migration capacity, were also verified in these cells. This study provided fundamentals for developing caprin-1 as a therapeutic target for the treatment of gliomas.

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Engineered T cells therapy holds promise for glioblastoma (GBM) therapy. Genetic modification of T-lymphocytes, using T cell receptors, chimeric antigen receptors, and others, is an attractive antitumor strategy, especially in large solid tumors. Recently, several clinical trials have shown an impressive tumor regression in GBM patients, demonstrating the therapeutic potential of this approach. Still, major challenges, such as antigen specificity, tumor trafficking, hostile immunosuppressive microenvironment, proliferation and persistence of T cells and unexpected adverse effects, may hinder the clinical benefit of this approach. In the present review, we summarize recent developments of engineered T cells therapy against GBM, its challenges and future.

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Background: Venous thromboembolism is a common complication in patients with glioma. The clotting factor von Willebrand factor (VWF) is a highly adhesive procoagulant molecule that mediates platelet adhesion to endothelial and subendothelial surfaces. In the current analysis, we examined The Cancer Genome Atlas (TCGA) data to assess the effect of VWF gene expression on prognosis in patients with lower grade gliomas (LGGs). Methods: For newly diagnosed gliomas, we evaluated the association between VWF and overall survival in the genomic data commons TCGA LGG dataset in TCGA. Survival data of the glioma subgroup were extracted for analysis and generation of Kaplan–Meier curves for overall survival. Results: Lower grade gliomas with less VWF gene expression had significantly better survival than those with more VWF gene expression (hazard ratio 0.64, 95% confidence interval 0.44–0.92, P = 0.015 log rank test). The effect of VWF gene expression on survival was even more evident when the sample was analyzed as three groups (P = 0.00019). IDH1, TP53, and ATRX mutations are present in 40% or more adult LGGs. Conclusion: The deleterious prognostic effect of VWF expression in LGGs is not surprising, given its role in other cancers. Therefore, VWF gene expression may be a clinically important risk marker in LGG.

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