The immune microenvironment in glioma is characterized by a complex interplay of various immune cell populations, particularly innate immune cells. A study by Sankowski utilized advanced techniques such as single-cell RNA sequencing and spatial transcriptomics to analyze over 356,000 transcriptomes from 102 individuals, revealing a diverse landscape of immune cells at the central nervous system (CNS) borders. This research highlighted the presence of CNS-associated macrophages (CAMs), which, despite their limited numbers, play a crucial role in the immune response within the brain. The findings suggest that these CAM subclasses exhibit temporal and spatial restrictions that could influence glioma progression and response to therapies (ref: Sankowski doi.org/10.1038/s41591-023-02673-1/). Furthermore, Stoller's investigation into glioblastoma using ferumoxytol and gadolinium-enhanced MRI revealed that the Fe contrast agent could delineate immune processes more effectively than traditional Gd-based imaging. The study found that the FLAIR+ Gd+ and Fe- imaging phenotypes did not express immune Hallmark gene sets, indicating that Fe contrast provides unique insights into the inflammatory processes associated with glioblastoma, thereby enhancing our understanding of tumor biology (ref: Stoller doi.org/10.1093/noajnl/).

Molecular diagnosis plays a pivotal role in the management of gliomas, particularly in guiding surgical resection and treatment strategies. Xie et al. developed a rapid intraoperative multi-molecular diagnostic approach utilizing ultrasound radio frequency signals combined with deep learning algorithms. Their study reported impressive diagnostic accuracies of 0.85 for IDH1, 0.84 for TERTp, and 0.88 for the 1p/19q co-deletion, with AUC values indicating robust performance across these biomarkers (ref: Xie doi.org/10.1016/j.ebiom.2023.104899/). This method promises to enhance the precision of glioma surgeries by enabling real-time molecular characterization. In contrast, Urcuyo's study protocol emphasizes the challenges of obtaining representative tumor samples due to the limited accessibility of brain tissue. The protocol aims to map the heterogeneity of brain tumors through image-localized biopsy techniques, addressing the shortcomings of standard tissue sampling methods that often fail to capture the full biological diversity of gliomas (ref: Urcuyo doi.org/10.1371/journal.pone.0287767/).

High-grade gliomas (HGGs) are notorious for their intratumoral heterogeneity, which complicates treatment and contributes to poor patient outcomes. Moffet's research utilized spatial technologies to construct a high-resolution molecular map of glioblastoma, revealing distinct domains of tumor heterogeneity. This study highlighted the diverse immune landscape within these spatially localized regions, suggesting that different areas of the tumor may respond differently to therapies (ref: Moffet doi.org/10.1093/noajnl/). The findings underscore the importance of understanding the spatial architecture of tumors in developing targeted treatment strategies. Additionally, Urcuyo's study protocol complements this theme by proposing a method to better capture the heterogeneity of brain tumors through image-localized biopsies, further emphasizing the need for innovative approaches to assess tumor diversity (ref: Urcuyo doi.org/10.1371/journal.pone.0287767/).

Spatial transcriptomics has emerged as a powerful tool in glioma research, enabling the dissection of tumor microenvironments at unprecedented resolution. Sankowski's study exemplifies this approach by combining single-cell RNA sequencing with spatial transcriptomics to characterize the immune landscape at CNS interfaces. The comprehensive analysis revealed significant insights into the distribution and function of immune cells, particularly CAMs, in relation to glioma pathology (ref: Sankowski doi.org/10.1038/s41591-023-02673-1/). Moffet's work further contributes to this theme by mapping the spatial architecture of high-grade gliomas, demonstrating how spatial technologies can elucidate the complex heterogeneity within tumors. This research not only highlights the diverse immune responses present but also suggests that spatial organization may influence treatment efficacy (ref: Moffet doi.org/10.1093/noajnl/). Together, these studies underscore the transformative potential of spatial transcriptomics in understanding glioma biology and improving therapeutic strategies.