The tumor microenvironment (TME) plays a crucial role in the progression of various cancers, particularly glioblastoma. Kloosterman et al. demonstrated that macrophages facilitate myelin recycling, which is essential for glioblastoma cells to meet their high metabolic demands. This study highlights the importance of lipid transfer from macrophages to cancer cells, suggesting potential metabolic vulnerabilities that could be targeted for therapeutic interventions (ref: Kloosterman doi.org/10.1016/j.cell.2024.07.030/). In another study, Jackson et al. explored the role of the cytokine Meteorin-like (METRNL) in T cell hypofunction within the TME, revealing that METRNL induces bioenergetic failure in CD8+ T cells, which could hinder the effectiveness of immunotherapies (ref: Jackson doi.org/10.1016/j.immuni.2024.07.003/). Additionally, Dobersalske et al. provided evidence of active lymphoid populations in cranial bone marrow adjacent to glioblastoma, challenging the notion of a uniformly immunosuppressed environment and suggesting that local immune responses may be more complex than previously thought (ref: Dobersalske doi.org/10.1038/s41591-024-03152-x/). Chen et al. further contributed to this theme by showing that ALOX5 promotes immunosuppressive M2 polarization in glioma-associated macrophages, indicating a significant role of lipid metabolism in immune modulation within the TME (ref: Chen doi.org/10.1136/jitc-2024-009492/). Overall, these studies underscore the intricate interplay between immune cells and tumor cells in the TME, revealing both challenges and opportunities for therapeutic strategies.

Recent research has significantly advanced our understanding of the molecular mechanisms underlying glioma progression. Yang et al. identified that thyroid hormone (TH) plays a pivotal role in promoting differentiation in medulloblastoma cells, suggesting that TH may counteract tumor growth by reversing the repression of differentiation markers (ref: Yang doi.org/10.1016/j.ccell.2024.07.008/). In a comprehensive analysis, Gupta et al. utilized single-cell transcriptomics to dissect the immune landscape of IDH-stratified gliomas, revealing distinct immune cell types that correlate with tumor genetics and treatment responses (ref: Gupta doi.org/10.1093/neuonc/). Zhao et al. highlighted the role of the proto-oncogene c-SRC in glioblastoma progression, demonstrating that mutations affecting fatty acid synthesis pathways can significantly impact tumor growth, thereby providing insights into potential metabolic targets for therapy (ref: Zhao doi.org/10.1038/s41467-024-51444-0/). Furthermore, Montoya et al. explored the effects of interferon regulatory factor 8 on the immune microenvironment in glioblastoma, showing that its modulation can enhance antitumor immunity and reduce immunosuppression (ref: Montoya doi.org/10.1093/neuonc/). Collectively, these studies illustrate the complex genetic and molecular landscape of gliomas, emphasizing the potential for targeted therapies that exploit these pathways.

Innovative therapeutic strategies are crucial for improving outcomes in patients with gliomas and other malignancies. Wang et al. conducted a large-scale analysis of meningiomas, identifying molecular classifications that can refine surgical and radiotherapeutic decision-making, thus enhancing treatment efficacy (ref: Wang doi.org/10.1038/s41591-024-03167-4/). In the context of lung cancer, Zhou et al. reported on a phase III trial demonstrating that the combination of gefitinib and anlotinib significantly improves progression-free survival in patients with EGFR-mutated non-small cell lung cancer, highlighting the benefits of dual-targeted therapies (ref: Zhou doi.org/10.1038/s41392-024-01927-9/). Furthermore, Lertsumitkul et al. and Martins et al. provided compelling evidence for the efficacy of EphA3-targeted CAR T-cell therapies against glioblastoma, showcasing their potential to generate robust antitumor responses in preclinical models (ref: Lertsumitkul doi.org/10.1136/jitc-2024-009486/; ref: Martins doi.org/10.1136/jitc-2024-009403/). These findings collectively underscore the importance of personalized and targeted approaches in cancer treatment, paving the way for improved patient outcomes.

Neuroinflammation plays a significant role in the pathology of gliomas and other brain tumors. Zhang et al. investigated the immune checkpoint CD73, revealing that its inhibition can enhance T cell infiltration and activity, thereby improving glioblastoma immunotherapy outcomes (ref: Zhang doi.org/10.1021/acsnano.4c04553/). This study highlights the potential of targeting metabolic checkpoints to overcome immune evasion in tumors. In a related study, Tripathi et al. identified TIM3 as a therapeutic target in pediatric gliomas, emphasizing the need for tailored immunotherapeutic strategies that consider the unique immune profiles of these tumors (ref: Tripathi doi.org/10.1172/JCI177413/). Additionally, the immune landscape of medulloblastoma was characterized by Yang et al., who identified tumor rejection antigens that could inform the development of antigen-directed therapies (ref: Yang doi.org/10.1186/s13073-024-01363-y/). These studies collectively illustrate the intricate relationship between neuroinflammation and tumor progression, suggesting that targeting immune pathways may enhance therapeutic efficacy in brain tumors.

The identification of clinical and prognostic biomarkers is essential for improving the management of gliomas and related malignancies. Teranishi et al. developed a targeted gene expression biomarker that predicts outcomes in meningiomas, demonstrating its utility in discriminating between local recurrence and overall survival (ref: Teranishi doi.org/10.1007/s00401-024-02791-1/). This biomarker showed a 5-year area under the curve (AUC) of 0.81 for local recurrence, highlighting its potential clinical relevance. Maas et al. further explored chromosomal alterations in meningiomas, finding that loss of chromosome 1p is associated with an increased risk of recurrence, thus providing a clinically applicable cut-off for risk stratification (ref: Maas doi.org/10.1007/s00401-024-02777-z/). Chen et al. examined the role of ALOX5 in glioma progression, linking oxylipin metabolism to immune modulation and suggesting that metabolic pathways may serve as prognostic indicators (ref: Chen doi.org/10.1136/jitc-2024-009492/). These findings emphasize the importance of integrating molecular and genetic data to enhance prognostic accuracy and inform treatment decisions.

Advancements in technologies and methodologies are revolutionizing the study and treatment of gliomas. Chokshi et al. utilized integrative genomic analyses to identify functional drivers of recurrent glioblastoma, revealing specific genetic dependencies that could inform targeted therapies (ref: Chokshi doi.org/10.1038/s41591-024-03138-9/). Roetzer-Pejrimovsky et al. applied deep learning techniques to link digital pathology phenotypes with transcriptional subtypes and patient outcomes in glioblastoma, showcasing the potential of artificial intelligence in enhancing diagnostic accuracy (ref: Roetzer-Pejrimovsky doi.org/10.1093/gigascience/). Banu et al. discovered a glioma cell state-specific metabolic vulnerability to ferroptosis, suggesting new therapeutic avenues for targeting metabolic pathways in glioblastoma (ref: Banu doi.org/10.1038/s44318-024-00176-4/). Furthermore, Luo et al. investigated the role of pericyte senescence in radiation-induced brain injury, highlighting a potential therapeutic target for mitigating cognitive decline in glioma patients (ref: Luo doi.org/10.1093/neuonc/). These studies collectively illustrate the transformative impact of innovative technologies on our understanding and treatment of gliomas.

The interplay between cancer and neural pathways is a critical area of investigation in understanding tumor behavior and therapeutic responses. Kloosterman et al. emphasized the role of macrophage-mediated myelin recycling in glioblastoma, illustrating how this crosstalk supports tumor metabolism and malignancy (ref: Kloosterman doi.org/10.1016/j.cell.2024.07.030/). Additionally, Soeung et al. explored the molecular landscape of epileptogenesis in glioblastoma, revealing how tumor-induced changes in the cortical microenvironment contribute to hyperexcitability and immune evasion (ref: Soeung doi.org/10.1016/j.xcrm.2024.101691/). Tripathi et al. identified TIM3 as a therapeutic target in pediatric gliomas, linking immune profiling to potential treatment strategies (ref: Tripathi doi.org/10.1172/JCI177413/). Furthermore, Banu et al. uncovered a metabolic vulnerability in glioma cells that could be exploited therapeutically, highlighting the significance of developmental pathways in tumor biology (ref: Banu doi.org/10.1038/s44318-024-00176-4/). These findings underscore the complexity of interactions between cancer and neural pathways, suggesting that targeting these interactions may enhance therapeutic efficacy.

Understanding the epidemiology and risk factors associated with gliomas and other cancers is crucial for developing preventive strategies. Lee et al. examined the impact of smoking habits post-cancer diagnosis on the risk of dementia, finding that initiators and relapsers had a significantly higher risk compared to sustained non-smokers (ref: Lee doi.org/10.1002/alz.14180/). This highlights the importance of smoking cessation in cancer survivors. Pan et al. investigated the role of glycogen metabolism in cholangiocarcinoma, identifying glycogen phosphorylase brain form (PYGB) as a prognostic indicator, which may inform future therapeutic approaches (ref: Pan doi.org/10.1158/0008-5472.CAN-24-0088/). Yang et al. explored the effects of thyroid hormone on medulloblastoma progression, suggesting that hormonal factors may influence tumor behavior (ref: Yang doi.org/10.1016/j.ccell.2024.07.008/). Kloosterman et al. further contributed to this theme by elucidating the metabolic interplay between glioblastoma and its microenvironment, suggesting that metabolic vulnerabilities could be targeted for prevention and treatment (ref: Kloosterman doi.org/10.1016/j.cell.2024.07.030/). These studies collectively emphasize the multifaceted nature of cancer risk factors and the need for integrated approaches to cancer prevention.