Gliomas are diffusely infiltrating brain tumors whose prognosis is strongly influenced by their extent of invasion into the surrounding brain tissue. While lower-grade gliomas present more circumscribed borders, high-grade gliomas are aggressive tumors with widespread brain infiltration and dissemination. Glioblastoma (GBM) is known for its high invasiveness and association with poor prognosis. Its low survival rate is due to the certainty of its recurrence, caused by microscopic brain infiltration which makes surgical eradication unattainable. New insights into GBM biology at the single-cell level have enabled the identification of mechanisms exploited by glioma cells for brain invasion. In this review, we explore the current understanding of several molecular pathways and mechanisms used by tumor cells to invade normal brain tissue. We address the intrinsic biological drivers of tumor cell invasion, by tackling how tumor cells interact with each other and with the tumor microenvironment (TME). We focus on the recently discovered neuronal niche in the TME, including local as well as distant neurons, contributing to glioma growth and invasion. We then address the mechanisms of invasion promoted by astrocytes and immune cells. Finally, we review the current literature on the therapeutic targeting of the molecular mechanisms of invasion.

Pediatric high-grade glioma (pHGG) encompasses a wide range of gliomas with different genomic, epigenomic, and transcriptomic features. Almost 50% of pHGGs present a mutation in genes coding for histone 3, including the subtype harboring the H3.3-G34 mutation. In this context, histone mutations are frequently associated with mutations in TP53 and ATRX, along with PDGFRA and NOTCH2NL amplifications. Moreover, the H3.3-G34 histone mutation induces epigenetic changes in immune-related genes and exerts modulatory functions on the microenvironment. Also, the functionality of the blood–brain barrier (BBB) has an impact on treatment response. The prognosis remains poor with conventional treatments, thus eliciting the investigation of additional and alternative therapies. Promising molecular targets include PDGFRA amplification, BRAF mutation, EGFR amplification, NF1 loss, and IDH mutation. Considering that pHGGs harboring the H3.3-G34R mutation appear to be more susceptible to immunotherapies (ITs), different options have been recently explored, including immune checkpoint inhibitors, antibody mediated IT, and Car-T cells. This review aims to summarize the knowledge concerning cancer biology and cancer-immune cell interaction in this set of pediatric gliomas, with a focus on possible therapeutic options.

Background: Technological advancements have been rapidly integrated within the neurosurgical education track since it is a high-risk specialty with little margin for error. Indeed, simulation and virtual reality during training can improve surgical performance and technical skills. Our study aims to investigate the impact of neurosurgical technology-based simulation activities on medical students. Methods and Materials: The “Suturing Mission–The Symposium” was a three-day event held at Humanitas University. Participants had access to live-streamed conferences held by worldwide experts in several fields of neurosurgery and practical simulations of dura mater sutures, microvascular anastomosis, and augmented reality neurosurgical approaches. An anonymous survey was conducted at the beginning and end of the event. Results: 141 medical students with a mean age of 21 participated. After the course, 110 participants (77.5%) showed interest in pursuing a surgical path, with a great prevalence in those who had planned to have a surgical career before the event (88.7% vs. 41.4%, p < 0.001). Participants were also asked about their comfort levels while handling surgical instruments, and a good outcome was reached in 72.7% of participants, with a significant difference between those who had previously attended a suture course (87.8% vs. 66.3%, p = 0.012). Conclusion: Training sessions on surgical simulators were effective in increasing participants’ interest in pursuing a surgical path, improving their understanding of postgraduate orientation, and boosting their confidence with surgical instruments.