Research in neurosurgery and brain tumors has increasingly focused on the interplay between tumor biology and immune response. A study by Fu et al. utilized single-cell RNA sequencing to investigate lung cancer brain metastasis (LCBM) and found that tyrosine kinase inhibitor (TKI) treatment elevates CTLA4 expression in T cells, fostering an immune-suppressive microenvironment (ref: Fu doi.org/10.1016/j.ccell.2024.09.012/). This highlights the challenges of TKI resistance in brain metastases. In the context of glioblastoma, Xia et al. developed CAR T cells with high-affinity protein binders targeting EGFR and CD276, demonstrating enhanced antitumor efficacy in vitro and in vivo (ref: Xia doi.org/10.1038/s41551-024-01258-8/). Additionally, Zhu et al. identified ROR1 as a key factor in glioblastoma stem cell proliferation, linking it to GRB2 and c-Fos expression, which may provide new therapeutic targets (ref: Zhu doi.org/10.1093/neuonc/). These studies collectively underscore the importance of targeting both tumor cells and the immune landscape to improve treatment outcomes in brain tumors. Moreover, the metabolic regulation of glioblastoma stem cells was explored by Lv et al., who showed that targeting malate dehydrogenase 2 (MDH2) reduced stem cell proliferation and tumor growth, indicating a potential metabolic vulnerability in glioblastoma (ref: Lv doi.org/10.1016/j.cmet.2024.09.014/). Duerinck et al. investigated the feasibility of intracranial administration of immune checkpoint inhibitors in recurrent high-grade glioma, reporting promising overall survival outcomes (ref: Duerinck doi.org/10.1093/neuonc/). Collectively, these findings highlight the multifaceted approaches required to tackle the complexities of brain tumors, emphasizing the integration of immunotherapy, metabolic targeting, and innovative surgical techniques.

The intersection of neuroimmunology and cancer has emerged as a critical area of research, particularly in understanding how tumors interact with the nervous system. Hwang et al. emphasized the need for a multidisciplinary approach to cancer neuroscience, identifying key priorities and challenges in translating findings to clinical practice (ref: Hwang doi.org/10.1016/j.ccell.2024.09.014/). This commentary sets the stage for further exploration of how neurobiological mechanisms can influence cancer progression and treatment responses. In a proteogenomic study, Hamilton et al. identified DLK1 as a promising immunotherapeutic target in neuroblastoma, highlighting the potential for targeted therapies in pediatric cancers (ref: Hamilton doi.org/10.1016/j.ccell.2024.10.003/). Moreover, the role of the immune microenvironment in glioblastoma was further elucidated by Israeli Dangoor et al., who demonstrated that CCL2 blockade combined with PD-1 immunomodulators could impede breast cancer brain metastasis, suggesting that astrocytes play a supportive role in tumor growth (ref: Israeli Dangoor doi.org/10.1093/brain/). Ku et al. explored the enhancement of CD8 T cell stemness through inhibitory Fcγ receptor deletion, which increased responsiveness to anti-PD-1 therapy in glioblastoma, indicating a potential strategy to overcome immune resistance (ref: Ku doi.org/10.1136/jitc-2024-009449/). These studies collectively illustrate the intricate relationship between the immune system and tumor biology, emphasizing the need for innovative therapeutic strategies that leverage this interplay.

Research into neurodegenerative diseases has increasingly focused on the molecular mechanisms underlying conditions such as Parkinson's disease and Alzheimer's disease. Bayati et al. developed a model of Parkinson's disease using human dopaminergic neurons exposed to α-synuclein fibrils and proinflammatory cytokines, revealing that immune-triggered lysosomal dysfunction may contribute to disease pathology (ref: Bayati doi.org/10.1038/s41593-024-01775-4/). This model provides a valuable platform for understanding the cellular mechanisms that lead to neurodegeneration. In a related study, Zhang et al. found that increased expression of mesencephalic astrocyte-derived neurotrophic factor (MANF) correlates with synapse loss in Alzheimer's disease, suggesting that MANF may play a detrimental role in synaptic integrity (ref: Zhang doi.org/10.1186/s13024-024-00771-3/). Additionally, Regoni et al. introduced a novel mouse model of juvenile parkinsonism linked to mutations in the PRKN gene, which could clarify the neurodegenerative processes and facilitate the development of neuroprotective strategies (ref: Regoni doi.org/10.1093/brain/). Furthermore, Lofredi et al. reported that striato-pallidal oscillatory connectivity correlates with symptom severity in dystonia patients, highlighting the importance of basal ganglia circuitry in movement disorders (ref: Lofredi doi.org/10.1038/s41467-024-52814-4/). Collectively, these findings underscore the importance of understanding the molecular and cellular underpinnings of neurodegenerative diseases to inform therapeutic development.

Advancements in neurosurgical techniques and innovations are pivotal for improving patient outcomes in various neurological conditions. A phase 3 trial by van As et al. demonstrated that stereotactic body radiotherapy (SBRT) is noninferior to conventional radiotherapy for localized prostate cancer, suggesting its efficacy as a treatment option (ref: van As doi.org/10.1056/NEJMoa2403365/). This trial underscores the importance of exploring alternative radiotherapy techniques in neurosurgery. In the realm of molecular imaging, Shaib et al. introduced one-step nanoscale expansion microscopy, achieving unprecedented resolution for visualizing individual proteins, which could revolutionize our understanding of protein interactions in the brain (ref: Shaib doi.org/10.1038/s41587-024-02431-9/). Moreover, Chang et al. developed Droplet Hi-C, a scalable method for profiling chromatin architecture in heterogeneous tissues, which could enhance our understanding of gene regulation in neurological disorders (ref: Chang doi.org/10.1038/s41587-024-02447-1/). Additionally, Song et al. presented SCOPE, a platform for amplifying extracellular vesicle mRNA detection, which could provide critical insights into tumor biology and patient management (ref: Song doi.org/10.1038/s41587-024-02426-6/). These innovations highlight the ongoing evolution of neurosurgical techniques and their potential to improve diagnostic and therapeutic strategies in neurology.

Neuroimaging and biomarker research is crucial for advancing our understanding of neurological disorders and improving diagnostic accuracy. Hamilton et al. identified DLK1 as an immunotherapeutic target in neuroblastoma through a comprehensive proteogenomic analysis, emphasizing the potential of biomarkers in guiding treatment decisions (ref: Hamilton doi.org/10.1016/j.ccell.2024.10.003/). In glioblastoma, Xia et al. reported on the development of CAR T cells with high-affinity protein binders, which could serve as a biomarker for therapeutic efficacy (ref: Xia doi.org/10.1038/s41551-024-01258-8/). Furthermore, Duerinck et al. explored the intracranial administration of immune checkpoint inhibitors, providing insights into the biomarkers associated with treatment response in recurrent high-grade glioma (ref: Duerinck doi.org/10.1093/neuonc/). Additionally, Petersen et al. employed lesion network mapping to assess white matter hyperintensity connectivity, revealing that higher connectivity scores are associated with lower cognitive performance, thus highlighting the potential of neuroimaging biomarkers in predicting cognitive outcomes (ref: Petersen doi.org/10.1093/brain/). The integration of these findings underscores the importance of neuroimaging and biomarker research in enhancing our understanding of neurological diseases and informing clinical practice.

Clinical outcomes and patient management strategies are critical in the context of neurological diseases and cancer treatment. Hamilton et al. highlighted the identification of DLK1 as an immunotherapeutic target in neuroblastoma, which could significantly impact treatment approaches for this aggressive pediatric cancer (ref: Hamilton doi.org/10.1016/j.ccell.2024.10.003/). In glioblastoma, Xia et al. reported on the development of CAR T cells with high-affinity protein binders, demonstrating improved antitumor performance and suggesting a new avenue for enhancing patient outcomes (ref: Xia doi.org/10.1038/s41551-024-01258-8/). Furthermore, Duerinck et al. investigated the feasibility of intracranial administration of immune checkpoint inhibitors in recurrent high-grade glioma, showing promising overall survival rates, which could inform future treatment protocols (ref: Duerinck doi.org/10.1093/neuonc/). Zhu et al. explored the role of ROR1 in glioblastoma growth, providing insights into potential therapeutic targets that could improve patient management strategies (ref: Zhu doi.org/10.1093/neuonc/). These studies collectively emphasize the importance of integrating innovative treatment strategies and understanding molecular mechanisms to enhance clinical outcomes in patients with neurological conditions.

Understanding the molecular mechanisms underlying neurosurgical interventions is essential for improving patient outcomes and developing targeted therapies. Hamilton et al. identified DLK1 as a significant immunotherapeutic target in neuroblastoma through an integrative proteogenomic analysis, highlighting the potential for targeted therapies in pediatric oncology (ref: Hamilton doi.org/10.1016/j.ccell.2024.10.003/). In glioblastoma, Xia et al. developed CAR T cells with high-affinity protein binders, demonstrating enhanced antitumor efficacy and providing insights into the molecular interactions that govern tumor response to immunotherapy (ref: Xia doi.org/10.1038/s41551-024-01258-8/). Moreover, Duerinck et al. explored the efficacy of intracranial administration of immune checkpoint inhibitors in recurrent high-grade glioma, revealing molecular pathways that could be targeted to improve treatment outcomes (ref: Duerinck doi.org/10.1093/neuonc/). Zhu et al. investigated the role of ROR1 in glioblastoma stem cell maintenance, linking it to critical signaling pathways that promote tumor growth (ref: Zhu doi.org/10.1093/neuonc/). These findings collectively underscore the importance of elucidating molecular mechanisms in neurosurgery to inform therapeutic strategies and enhance patient management.