bims-malgli Biomed News
on Biology of malignant gliomas
Issue of 2026–02–01
five papers selected by
Oltea Sampetrean, Keio University
  1. Recent advances in immunotherapy for gliomas: overcoming barriers and advancing precision strategies.
  2. Muribaculum intestinalenegatively impacts glioma growth in mice through the toll-like receptor 2.
  3. Mechanism of Glioblastoma Treatment Targeting Growth Factors: IGF-I Case Using Gene, Immune, Phytochemicals, and Nanotechnologies.
  4. Mitochondrial protein carboxyl-terminal alanine-threonine tailing promotes human glioblastoma growth by regulating mitochondrial function.
  5. Oligodendrocyte transcription factor 2 orchestrates glioblastoma immune evasion by suppressing CXCL10 and CD8+ T cell activation.
  1. Front Immunol. 2025 ;16 1690464
    Recent advances in immunotherapy for gliomas: overcoming barriers and advancing precision strategies.
    Abdullah Jabri, Abdulaziz Mhannayeh, Bader Taftafa, Mohamed Alsharif, Dania Sibai, Raghad Alsharif, Tasnim Abbad, Abdulrahman Elsalti, Zara Ahmed, Jahan Salma, Mohammed Imran Khan, Ahmed Yaqinuddin.
      Gliomas, and particularly glioblastoma (GBM), remain among the most lethal primary brain tumors, with outcomes constrained by extensive intra tumor heterogeneity, a profoundly immunosuppressive tumor microenvironment (TME), and the restrictive nature of the blood-brain barrier (BBB). Although immunotherapies, including immune checkpoint inhibitors, chimeric antigen receptor (CAR) T and NK cells, and oncolytic virotherapy, have redefined treatment paradigms in other malignancies, their efficacy in gliomas has been modest, limited by low tumor mutational burden, antigenic plasticity, metabolic suppression, and therapy-associated immunosuppression. Recent advances in multi-antigen targeting, metabolic reprogramming, and innovative delivery strategies have enhanced preclinical efficacy, while the integration of emerging biomarkers such as ADAMTSL4, ACSS3, and radiomics-derived immune signatures offers opportunities for precision patient stratification. Converging developments in real-time molecular monitoring, spatial immunoprofiling, and rationally designed combination regimens hold the potential to recalibrate the glioma immune landscape, paving the way toward clinically impactful and durable immunotherapeutic responses.
    Keywords:  glioblastoma; glioma; immune checkpoint inhibitors; immunotherapy; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2025.1690464
  2. Gut Microbes. 2026 Dec 31. 18(1): 2623349
    Muribaculum intestinalenegatively impacts glioma growth in mice through the toll-like receptor 2.
    Francesco Marrocco, Germana Cocozza, Fabrizio Antonangeli, Rizwan Khan, Giuseppe Pietropaolo, Abdechakour Elkihel, Gabriele Favaretto, Xingzi Lin, Romina Mancinelli, Ludovica Maria Busdraghi, Alice Reccagni, Gianluca Scarno, Giuseppe Sciumè, Mattia Laffranchi, Ling Peng, Valerio Iebba, Silvano Sozzani, Giuseppina D'Alessandro, Cristina Limatola.
      Glioblastoma (GBM) is the most common and malignant brain tumor in adult humans. Recent studies have demonstrated a link between the composition of the gut microbiota and glioma progression. Here, we describe that the growth of glioma in mice is inversely correlated with the relative abundance of the anaerobic bacterium Muribaculum intestinale in the feces. We found that M. intestinale administration: 1) induced an inflammatory environment in the gut; 2) reduced glioma growth; 3) increased the pro-inflammatory profile of tumor-associated microglial cells and the frequency of CD8+ T cells; and 4) increased the peripheral TNF-α levels. The effects induced by M. intestinale administration were significantly attenuated upon toll-like receptor 2 (TLR2) silencing using TLR2-targeting siRNA. As a pattern-recognition receptor, TLR2 detects microbial-associated molecular patterns and orchestrates host immune responses to infection. Collectively, these data demonstrate that M. intestinale induces a pro-inflammatory response in glioma bearing mice, inhibiting tumor growth via TLR2-dependent signaling.
    Keywords:  Glioma; Muribaculum intestinale; gut microbiota; immune cell activation
    DOI:  https://doi.org/10.1080/19490976.2026.2623349
  3. CNS Neurol Disord Drug Targets. 2026 Jan 15.
    Mechanism of Glioblastoma Treatment Targeting Growth Factors: IGF-I Case Using Gene, Immune, Phytochemicals, and Nanotechnologies.
    Gabriela Quintero, Maryam Raja, Annabelle Trojan, Yu-Chun Lone, Jerzy Trojan.
      Glioblastoma multiforme (GBM), a fatal malignant brain tumor, represents a challenge in terms of developing new treatments. Solutions have been proposed in connection with anti-tumor immune responses, generally T cell strategies, including techniques targeting growth factors, particularly IGF-I, the primary cancer growth factor, and its signal transduction pathways. The objective of this review is to assess the immunogene mechanism targeting IGF-I, which constitutes the basis of the described cancer gene therapy for GBM, stemming from brain neoplastic development studies. The GBM gene therapy, based on new strategies of anti-gene IGF-I techniques, including antisense or triple helix, has been combined with phytochemicals (phenolics) and nanotechnologies (theranostic nanoparticles). The three approaches have modulated IGF-I expression together, inducing common signal transduction pathways: IGF-I-R, TK/PI3K/AKT/TLR/MAPK & JAK/STAT. These signals have transformed in vitro neoplastic glioma cells into immunogenic cells. These immunogenic cells, which express MHC-1 and B7, produce a strong T CD8 anti-tumour immune response after in vivo injection. The combined strategy of anti-IGF-I/phytochemical/nanotechnology vaccines has shown promising clinical results, with patient survival of up to two and three years in some cases. The obtained results are discussed in parallel with other immunotherapies and antitumour vaccine studies that involve the immunogenicity mechanism.
    Keywords:  CNS and glioblastoma; IGF-I; cancer gene therapy; growth factors; nanotechnology.; phytochemicals; signal transduction pathways
    DOI:  https://doi.org/10.2174/0118715273368842251113060453
  4. Elife. 2026 Jan 29. pii: RP99438. [Epub ahead of print]13
    Mitochondrial protein carboxyl-terminal alanine-threonine tailing promotes human glioblastoma growth by regulating mitochondrial function.
    Bei Zhang, Ting Cai, Esha Reddy, Yuanna Wu, Isha Mondal, Yinglu Tang, Adaeze Scholastical Gbufor, Jerry Wang, Yawei Shen, Qing Liu, Raymond Sun, Winson S Ho, Rongze Olivia Lu, Zhihao Wu.
      The rapid and sustained proliferation of cancer cells necessitates increased protein production, which, along with their disrupted metabolism, elevates the likelihood of translation errors. Ribosome-associated quality control (RQC), a recently identified mechanism, mitigates ribosome collisions resulting from frequent translation stalls. However, the precise pathophysiological role of the RQC pathway in oncogenesis remains ambiguous. Our research centered on the pathogenic implications of mitochondrial stress-induced protein carboxyl-terminal alanine and threonine tailing (msiCAT-tailing), a specific RQC response to translational arrest on the outer mitochondrial membrane, in human glioblastoma multiforme (GBM). The presence of msiCAT-tailed mitochondrial proteins was observed commonly in glioblastoma stem cells (GSCs). The exogenous introduction of the mitochondrial ATP synthase F1 subunit alpha (ATP5α) protein, accompanied by artificial CAT-tail mimicking sequences, enhanced mitochondrial membrane potential (ΔΨm) and inhibited the formation of the mitochondrial permeability transition pore (MPTP). These alterations in mitochondrial characteristics provided resistance to staurosporine (STS)-induced apoptosis in GBM cells. Consequently, msiCAT-tailing can foster cell survival and migration, whereas blocking msiCAT-tailing via genetic or pharmacological intervention can impede GBM cell overgrowth.
    Keywords:  cancer biology; carboxyl-terminal alanine and threonine tailing; cell biology; glioblastoma; human; mitochondria; ribosome-associated quality control
    DOI:  https://doi.org/10.7554/eLife.99438
  5. J Clin Invest. 2026 Jan 27. pii: e195556. [Epub ahead of print]
    Oligodendrocyte transcription factor 2 orchestrates glioblastoma immune evasion by suppressing CXCL10 and CD8+ T cell activation.
    Xinchun Zhang, Jinjiang Xue, Cunyan Zhao, Chenqiuyue Zeng, Jiacheng Zhong, Gangfeng Yu, Xi Yang, Yao Ling, Dazhen Li, Jiaxiao Yang, Yun Xiu, Hongda Li, Shiyuan Hong, Liangjun Qiao, Song Chen, Q Richard Lu, Yaqi Deng, Zhaohua Tang, Fanghui Lu.
      Glioblastoma (GBM) is a highly lethal brain tumor with limited treatment options and resistance to immune checkpoint inhibitors due to its immunosuppressive tumor microenvironment (TME). Here, we identify OLIG2 as a key regulator of immune evasion in GBM stem-like cells, inhibiting CD8+ T cell-dependent antitumor immunity, while promoting pro-tumor macrophages polarization. Mechanistically, OLIG2 recruits HDAC7 to repress CXCL10 transcription, inducing STAT3 activation in tumor-associated macrophages (TAMs) and decreasing CD8+ T cell infiltration and activation. Genetic deletion of OLIG2 significantly increases CXCL10 secretion, shifting TAMs toward an anti-tumor phenotype and enhancing CD8+ T cell activities. Furthermore, upregulated OLIG2 expression is correlated to resistance to immune checkpoint inhibitors (ICIs) in GBM patients. OLIG2 inhibition by either genetic deficiency or pharmacological targeting with CT-179 sensitizes GBM tumors to anti-PD-L1 therapy, enhancing antitumor immune responses and prolonging survival. Our findings reveal OLIG2+ glioma stem-like cells as critical mediators of immune evasion and identify the OLIG2/HDAC7/CXCL10 axis as a potential therapeutic target to enhance immune checkpoint inhibitors efficacy and to improve immunotherapy outcomes in aggressive GBM.
    Keywords:  Brain cancer; Cell biology; Immunology; Oncology
    DOI:  https://doi.org/10.1172/JCI195556
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