bims-malgli 2026-08-30 papers

Issue of 2026–08–30
five papers selected by
Oltea Sampetrean, Keio University

Nat Cancer. 2026 Aug 25.

Galanin impairs tumor immunity in glioblastoma by promoting infiltration and ferroptosis resistance of myeloid-derived suppressor cells.

Lizhi Pang, Yang Liu, Fei Zhou, Songlin Guo, Fatima Khan, Heba Ali, Hardik Shah, Sara Huber, Barbara Kofler, Craig M Horbinski, Peiwen Chen.

Glioblastoma (GBM) is a highly aggressive and lethal form of brain tumor that resists immunotherapy. Here we show that neuropeptide galanin (GAL) drives immunosuppression and immunotherapy resistance in GBM. Mechanistically, GBM cell-secreted GAL interacts with its receptor GALR3 on monocytic myeloid-derived suppressor cells (mMDSCs), triggering USP51-mediated deubiquitination of estrogen receptor-α, thereby engaging membrane-bound O-acyltransferase domain-containing 1 signaling. This signaling cascade, in turn, promotes the infiltration of immunosuppressive mMDSCs and confers ferroptosis resistance to them in the tumor microenvironment. Targeting mMDSCs through GALR3 inhibition and ferroptosis induction impairs tumor progression and activates antitumor immunity in GBM mouse models. Remarkably, combining this approach with anti-PD1 therapy achieves durable and complete tumor regression in approximately 60% of tumor-bearing mice. Our study elucidates the molecular mechanism underlying GBM immunosuppression and highlights a promising therapeutic strategy to enhance GBM response to immunotherapy.

DOI: https://doi.org/10.1038/s43018-026-01221-3

Neurooncol Adv. 2026 Jan-Dec;8(1):8(1): vdag203

Stem-like TCF1+CD8+ T cells are associated with improved survival in male glioblastoma patients.

Juyeun Lee, Jesper Dupont Ewald, Rikke H Dahlrot, Arnon Møldrup Knudsen, Justin D Lathia, Bjarne Winther Kristensen.

Glioblastoma (GBM) exhibits a significant male bias, characterized by higher incidence and worse clinical outcomes. Tumor-intrinsic and extrinsic factors, including the immune system, contribute to these differences, yet the precise mechanisms and clinical implications remain elusive. We previously identified an increased frequency of stem-like/progenitor-exhausted TCF1+CD8+ T cells in male GBM mouse models and human patients, which may contribute to these sex differences. In this study, we sought to determine the clinical significance of stem-like TCF1+CD8+ T cells in GBM and their potential to influence survival outcomes in a sex-dependent manner.

Keywords: glioblastoma; sex differences; stem-like CD8+ T cells

DOI: https://doi.org/10.1093/noajnl/vdag203

Hum Cell. 2026 Aug 24. pii: 130. [Epub ahead of print]39(9):

Mitochondria and exosome intercellular co-transfer via annular gap junction vesicles in the human glioblastoma stem cell niche.

Gabriel Arismendi-Morillo.

Keywords: Annular gap junction vesicles; Exosomes; Glioblastoma; Mitochondrial transfer

DOI: https://doi.org/10.1007/s13577-026-01437-6

J Clin Med. 2026 Aug 18. pii: 6387. [Epub ahead of print]15(16):

IDH-Mutant Diffuse Glioma: From Metabolic Origins to Targeted Therapy.

Tadeja Urbanic-Purkart.

Background/Objectives: Isocitrate Dehydrogenase (IDH)1/2-mutant diffuse gliomas represent a biologically distinct subgroup of adult brain tumors in which eary metabolic reprogramming and accumulation of the oncometabolite D-2-hydroxyglutarate (D-2HG) drive epigenetic, immunologic, and clinical characteristics, including a high burden of glioma-associated epilepsy. This review summarizes the molecular and metabolic consequences of IDH mutations, their role in glioma-associated epilepsy, and the evolving impact of mutant IDH-targeted therapies in contemporary neuro-oncology. Methods: We conducted a narrative review of key molecular, translational, imaging, and clinical studies on IDH-mutant diffuse gliomas. The literature included the 2021 (World Health Organization) WHO Classification of Tumours of the Central Nervous System, studies investigating D-2HG biology and glioma-associated epilepsy, and prospective clinical trials and real-world evidence evaluating IDH-targeted therapies and contemporary antiseizure management. Particular emphasis was placed on vorasidenib, advanced metabolic imaging, and emerging liquid biopsy approaches. Results: IDH mutations are early driver events that promote D-2HG accumulation, resulting in widespread epigenetic reprogramming, metabolic dysregulation, and an immunosuppressive tumor microenvironment. D-2HG has also been implicated in the development of glioma-associated epilepsy, although the underlying mechanisms remain incompletely understood. Advances in integrated histomolecular diagnostics, magnetic resonance spectroscopy, amino acid positron emission tomography, and cerebrospinal fluid liquid biopsy have improved disease classification and treatment monitoring. Mutant IDH inhibitors, particularly vorasidenib, prolong progression-free survival, delay the need for subsequent treatment, and reduce intratumoral D-2HG concentrations, and have shown encouraging early signals of improved seizure control and preserved health-related quality of life in patients with grade 2 IDH-mutant gliomas, although this evidence remains preliminary and requires confirmation in larger prospective studies. Conclusions: IDH-mutant diffuse gliomas exemplify precision neuro-oncology, in which a single metabolic alteration informs diagnosis, disease monitoring, and targeted therapeutic approach. Additionally, ongoing studies are expected to further define the role of IDH inhibition across different disease stages and in combination with immunotherapy and standard treatments. Lastly, future clinical trials should systematically incorporate seizure outcomes, neurocognitive function, patient-reported outcomes, and immunologic endpoints to optimize both tumor control and quality of life.

Keywords: D-2-hydroxyglutarate; IDH-mutant diffuse glioma; glioma-associated epilepsy; precision neuro-oncology; vorasidenib

DOI: https://doi.org/10.3390/jcm15166387