The tumor microenvironment (TME) plays a crucial role in cancer progression and immune evasion. Recent studies have highlighted how ovarian tumor cells can gain a competitive advantage by actively reducing the fitness of surrounding microenvironment cells through the exosome-mediated release of a long non-coding RNA, Tu-Stroma, which alters the splicing of the Flower gene in TME cells, leading to a fitness decline (ref: Madan doi.org/10.1038/s41587-024-02453-3/). Additionally, the interplay between B cells and T cells has been shown to influence autoimmunity and lymphomagenesis, with findings indicating that B cells with moderate stimulation sensitivity can lead to fatal autoimmune pathology, while those with high sensitivity do not (ref: Diehl doi.org/10.1016/j.immuni.2024.11.023/). Furthermore, antigen presentation by tumor-associated macrophages has been linked to T cell exhaustion, with a defined metric indicating that the ratio of progenitor to terminally exhausted T cells decreases with tumor progression, suggesting a potential target for immunotherapy (ref: Waibl Polania doi.org/10.1016/j.immuni.2024.11.026/). RORc-expressing immune cells have also been identified as negative regulators of tertiary lymphoid structures, which are critical for anti-tumor immunity, thereby promoting tumor development (ref: Cinnamon doi.org/10.1016/j.jhep.2024.12.015/). In glioblastoma, tumor-associated microglia and a distinct neutrophil subpopulation have been shown to support tumor progression, highlighting the complex immune landscape of this aggressive cancer (ref: Wu doi.org/10.1158/0008-5472.CAN-24-0018/; ref: Zhao doi.org/10.1016/j.celrep.2024.115014/).

Innovative therapeutic strategies are emerging to tackle the challenges posed by glioblastoma. Patient-derived glioblastoma organoids have been utilized as real-time avatars to assess responses to CAR-T cell therapy, demonstrating early efficacy signals in a phase 1 study (ref: Logun doi.org/10.1016/j.stem.2024.11.010/). Additionally, the development of an NIR-II two-photon excitable photosensitizer has shown promise in treating small-size glioblastomas, addressing the issue of residual tumors post-surgery (ref: Xu doi.org/10.1002/adma.202413164/). A novel vascularized tumor organoid-on-a-chip model has been introduced to better study tumor-vascular dynamics and therapeutic responses, enhancing the physiological relevance of organoid studies (ref: Du doi.org/10.1002/adma.202412815/). Neoadjuvant anti-PD1 immunotherapy has also been explored, revealing a unique molecular signature associated with improved survival in recurrent glioblastoma patients (ref: McFaline-Figueroa doi.org/10.1038/s41467-024-54326-7/). Furthermore, the identification of a tri-specific T-cell engager targeting IL-13Rα2 and EGFRvIII has shown potential in promoting antitumor cytotoxicity and long-term survival in heterogeneous glioblastoma challenges (ref: Park doi.org/10.1136/jitc-2024-009604/).

The genomic landscape of gliomas is being increasingly elucidated through advanced molecular characterization techniques. A multi-cohort study has revealed the prevalence and implications of primary mismatch repair deficiency (MMRD) in gliomas among children, adolescents, and young adults, highlighting unique biology and therapeutic opportunities (ref: Negm doi.org/10.1016/S1470-2045(24)00640-5/). Additionally, the use of cell-free DNA (cfDNA) and serial tumor sequencing has uncovered subtype-specific cancer evolution and epigenetic states, providing insights into the genetic drivers of aggressive pediatric cancers (ref: George doi.org/10.1158/2159-8290.CD-24-0916/). Longitudinal monitoring via cerebrospinal fluid (CSF) collection has also been explored, offering a novel approach to assess glioma responses to treatment (ref: Riviere-Cazaux doi.org/10.1158/1078-0432.CCR-24-1814/). Furthermore, the integration of deep learning with histological images has shown promise in predicting gene mutations in lung cancer, underscoring the potential of machine learning in genomic characterization (ref: Zhao doi.org/10.1016/S1470-2045(24)00599-0/).

Research in neural and stem cell biology is shedding light on tumor progression mechanisms. A framework for neural organoids and assembloids has been proposed to enhance reproducibility and utility in modeling human development and disease (ref: Pașca doi.org/10.1038/s41586-024-08487-6/). Daily glucocorticoids have been shown to influence glioblastoma growth and synchronize tumor circadian rhythms with the host, indicating a complex interplay between host signaling and tumor biology (ref: Gonzalez-Aponte doi.org/10.1016/j.ccell.2024.11.012/). Additionally, macrophage-mediated myelin recycling has been identified as a mechanism promoting glioblastoma progression, emphasizing the role of cellular interactions in tumor microenvironments (ref: Pagano Zottola doi.org/10.1038/s41392-024-02055-0/). The engineering of tissue-sensing T cells for targeted therapy delivery to the brain has also shown potential in enhancing treatment efficacy against glioblastoma (ref: Simic doi.org/10.1126/science.adl4237/).

Clinical outcomes in glioblastoma are being closely examined to improve patient management strategies. A study focusing on the peritumoral brain zone has highlighted the spatial heterogeneity associated with glioblastoma recurrences, suggesting that targeted assessments of this area could enhance treatment strategies (ref: Wang doi.org/10.1038/s41467-024-55243-5/). The use of cfDNA sequencing has proven valuable in identifying genetic and epigenetic drivers of relapse in pediatric tumors, emphasizing the need for personalized treatment approaches (ref: George doi.org/10.1158/2159-8290.CD-24-0916/). Moreover, the efficacy of neoadjuvant pembrolizumab in recurrent glioblastoma has been linked to a specific cell cycle gene signature, which serves as a positive risk factor for survival (ref: McFaline-Figueroa doi.org/10.1038/s41467-024-54326-7/). The transition of T cells from a progenitor exhaustion state to terminal exhaustion has been characterized, providing insights into immunotherapeutic responsivity (ref: Waibl Polania doi.org/10.1016/j.immuni.2024.11.026/).

Advancements in imaging and diagnostic techniques are critical for improving glioblastoma management. The development of real-time viscoelastic deformability cytometry has enabled high-throughput mechanical phenotyping of liquid and solid biopsies, facilitating the detection and classification of cancerous cells (ref: Asghari doi.org/10.1126/sciadv.abj1133/). Daily glucocorticoids have been shown to influence glioblastoma growth patterns, suggesting that circadian rhythms may be an important factor in tumor behavior (ref: Gonzalez-Aponte doi.org/10.1016/j.ccell.2024.11.012/). The integration of RNA sequencing and cfDNA analysis has provided insights into subtype-specific cancer evolution and epigenetic states, enhancing the understanding of glioma biology (ref: George doi.org/10.1158/2159-8290.CD-24-0916/). Furthermore, the novel DNA cross-linking agent KL-50 has demonstrated significant efficacy against patient-derived glioblastoma models, indicating its potential as a therapeutic option (ref: McCord doi.org/10.1093/neuonc/).

Metabolic pathways are increasingly recognized for their role in tumor biology and treatment resistance. Research has shown that metabolic nanoregulators can induce ferroptosis and alter metabolite flow, potentially reversing the immunosuppressive tumor microenvironment (ref: Wang doi.org/10.1021/acsnano.4c13425/). A dual-targeted biomimetic liposomal system has been developed to interrupt carcinoma-astrocyte gap junctions, aiming to attenuate chemoresistance in brain metastases (ref: Cheng doi.org/10.1021/acsnano.4c09996/). Additionally, drug-device-field integration strategies targeting mitochondrial dysfunction have been proposed to enhance tumor therapy while minimizing invasiveness (ref: Liu doi.org/10.1016/j.biomaterials.2024.122990/). The ferritin-based supramolecular assembly drug delivery system has emerged as a promising approach to enhance the tumor-targeted therapy of aminated fullerene derivatives, addressing toxicity concerns (ref: Zhang doi.org/10.1002/advs.202413389/).

Neuro-oncology research is increasingly focusing on pediatric considerations, particularly regarding gliomas. A multi-cohort study has characterized primary mismatch repair deficiency (MMRD) in gliomas among children and young adults, revealing unique biological features and therapeutic implications (ref: Negm doi.org/10.1016/S1470-2045(24)00640-5/). The use of cfDNA and serial tumor sequencing has highlighted the genetic and epigenetic drivers of aggressive pediatric cancers, providing insights into potential therapeutic targets (ref: George doi.org/10.1158/2159-8290.CD-24-0916/). Additionally, the development of novel therapeutic strategies, such as two-photon photodynamic therapy, aims to address the challenges of residual tumors post-surgery in glioblastoma (ref: Xu doi.org/10.1002/adma.202413164/). Longitudinal monitoring via cerebrospinal fluid collection has also been explored as a method to assess treatment responses in gliomas, enhancing patient management strategies (ref: Riviere-Cazaux doi.org/10.1158/1078-0432.CCR-24-1814/).