Although reactive astrocytes constitute a major component of the cellular environment in glioblastoma, their function and crosstalk to other components of the environment is still poorly understood. Gene expression analysis of purified astrocytes from both the tumor core and non-infiltrated cortex reveals a tumor-related up-regulation of Chitinase 3-like 1 (CHI3L1), a cytokine which is related to inflammation, extracellular tissue remodeling, and fibrosis. Further, we established and validated a co-culture model to investigate the impact of reactive astrocytes within the tumor microenvironment. Here we show that reactive astrocytes promote a subtype-shift of glioblastoma towards the mesenchymal phenotype, driving mitogen-activated protein kinases (MAPK) signaling as well as increased proliferation and migration. In addition, we demonstrate that MAPK signaling is directly caused by a CHI3L1-IL13RA2 co-binding, which leads to increased downstream MAPK and AKT signaling. This novel microenvironmental crosstalk highlights the crucial role of non-neoplastic cells in malignant brain tumors and opens up new perspectives for targeted therapies in glioblastoma.

Gap junctions have recently been shown to interconnect glioblastoma cells to a multicellular syncytial network, thereby allowing intercellular communication over long distances as well as enabling glioblastoma cells to form routes for brain microinvasion. Against this backdrop gap junction-targeted therapies might provide for an essential contribution to isolate cancer cells within the brain, thus increasing the tumor cells’ vulnerability to the standard chemotherapeutic agent temozolomide. By utilizing INI-0602—a novel gap junction inhibitor optimized for crossing the blood brain barrier—in an oncological setting, the present study was aimed at evaluating the potential of gap junction-targeted therapy on primary human glioblastoma cell populations. Pharmacological inhibition of gap junctions profoundly sensitized primary glioblastoma cells to temozolomide-mediated cell death. On the molecular level, gap junction inhibition was associated with elevated activity of the JNK signaling pathway. With the use of a novel gap junction inhibitor capable of crossing the blood–brain barrier—thus constituting an auspicious drug for clinical applicability—these results may constitute a promising new therapeutic strategy in the field of current translational glioblastoma research.

Background: Falcotentorial meningiomas are exceptionally uncommon tumors, presenting a challenge for neurosurgeons due to their close proximity to vital structures. Gross total resection represents the standard of treatment for these tumors. However, care must be taken when surgically approaching these lesions, since damaging neurovascular structures may cause unacceptable morbidity. Selecting the optimal surgical approach for each tumor is of paramount importance when treating these patients. Methods: The authors reviewed medical records to identify all patients with falcotentorial meningiomas who underwent resection at the University Hospital of Freiburg between January 2001 and December 2021. Clinical and imaging data, surgical management, and clinical outcomes were analyzed. Results: Falcotentorial meningiomas occurred in 0.7% (15 of 2124 patients) of patients with intracranial meningiomas. Of these 15 patients, 8 were female and 7 male. The occipital interhemispheric approach was used in nine patients, the supracerebellar infratentorial approach in five patients, and the retrosigmoidal approach in one patient. Three patients developed visual field deficits after surgical resection. Incomplete resection was significantly associated with tumor progression (p < 0.05). Conclusions: Individualized surgical strategies, guided by preoperative imaging and classification systems, play a crucial role in optimizing patient care. Among the available approaches, the occipital interhemispheric and supracerebellar infratentorial approaches are frequently employed and considered among the safest options for these tumors.

Summary: The diversity of molecular states and cellular plasticity of immune cells in the glioblastoma environment is still poorly understood. Here, we performed scRNA sequencing of the immune compartment and mapped potential cellular interactions leading to an immunosuppressive microenvironment and dysfunction of T cells. Through inferring the dynamic adaptation during T cell activation, we identified three different terminal states with unique transcriptional programs. Modeling of driver genes for terminal T cell fate identified IL-10 signaling alterations in a subpopulation of HAVCR2(+) T cells. To explore in depth cellular interactions, we established an in-silico model by the integration of spatial transcriptomic and scRNA-sequencing, and identified a subset of HMOX1 ⁺ myeloid cells defined by IL10 release leading to T cell exhaustion. We found a spatial overlap between HMOX(+) myeloid and HAVCR2(+) T cells, suggesting that myeloid-lymphoid interaction causes immunosuppression present in tumor regions with enriched mesenchymal gene expression. Using human neocortical GBM model, coupled with patient-derived T cells, we confirmed that the functional interaction between myeloid and lymphoid cells, leads to a dysfunctional state of T cells. This IL-10 driven T cell exhaustion was found to be rescued by JAK/STAT inhibition. A comprehensive understanding of the cellular states and plasticity of lymphoid cells in GBM will aid towards successful immunotherapeutic approaches.

Background: Oligodendroglioma (ODG) are CNS resistant tumors characterized by their unique molecular signature, namely a combined deletion of 1p and 19q simultaneously to an IDH1/2 mutation. These tumors have a more favorable clinical outcome compared to other gliomas and a long-time survival that ranges between 10-20 years. However, during the course of the disease, multiple recurrences occur and the optimal treatment at each stage of the disease remains unclear. Here we report a retrospective longitudinal observation study of 836 MRI examinations in 44 ODG patients. Methods: We quantified the volume of T2-hyperintensity to compute growth behavior in dependence of different treatment modalities, using various computational models. Results: The identified growth pattern revealed dynamic changes, which were found to be patient-specific an did not correlate with clinical parameter or therapeutic interventions. Further, we showed that, surgical resection is beneficial for overall survival regardless the WHO grad or timepoint of surgery. To improve overall survival, an extent of resection above 50% is required. Multiple resections do not generally improve overall survival, except a greater extent of resection than in previous surgeries was achieved. Conclusions: Our data aids to improve the interpretation of MRI images in clinical practice.

Background/Objectives: Reconstructed three-dimensional (3D) endoscopic visualization is believed to improve depth perception and surgical performance compared with conventional two-dimensional (2D) systems. However, evidence supporting its use in unilateral biportal endoscopic (UBE) spine surgery remains limited. The objective was to compare procedural performance, task completion times, and subjective workload between 3D and 2D visualization in simulated biportal lumbar endoscopy. Methods: This randomized crossover pilot feasibility ex vivo study enrolled 6 neurosurgeons (3 residents, 3 seniors) who each completed a standardized UBE lumbar discectomy simulation (UpSurgeOn Lumbar SpineBox) under both 3D and 2D visualization in randomized sequence. The primary outcome was composite procedural performance (0–100 scale) assessed using a multi-item checklist encompassing technical success, quality, and safety. Secondary outcomes included task completion times for 7 procedural steps and subjective workload. Linear mixed-effects models adjusted for expertise level, spinal segment, operative side, and session order. Within-participant effect sizes (Cohen’s d) and a sensitivity power analysis were calculated. Results: All participants completed both conditions (24 procedures). Composite performance was high with both modalities, with no significant difference for the unweighted (adjusted difference 0.64 points, 95% CI −3.67 to 4.96, p = 0.76, d = 0.13) or weighted score (1.67 points, 95% CI −4.04 to 7.37, p = 0.55, d = 0.26). Subjective workload also did not differ (p = 0.67, d = 0.19). Effect sizes were negligible to small for most outcomes but reached medium magnitude for subjective fatigue (d = 0.54) and situational stress (d = 0.56). Exploratory expertise-stratified comparisons suggested faster lamina drilling with 3D among seniors (p = 0.04) and slower dura identification with 3D among residents (p = 0.02), based on only 3 participants per subgroup. The sample afforded 80% power to detect only very large effects (d ≈ 1.43). Conclusions: 3D visualization was feasible and well tolerated but did not significantly improve procedural performance, task completion time, or subjective workload in UBE simulation. Because the study was powered to detect only very large effects, these nonsignificant results reflect limited power rather than equivalence, and the medium effect-size signals for fatigue and situational stress are hypothesis-generating. Adequately powered trials are needed to confirm task-specific or expertise-dependent benefits.