Glioblastoma, an aggressive primary brain tumor, relies on metabolic and immunological remodeling of its tumor microenvironment for progression and therapeutic resistance. Tumor-associated macrophages (TAMs), including resident microglia and infiltrating monocyte-derived macrophages, represent abundant immune populations within this environment. While microglia normally maintain central nervous system homeostasis through immune surveillance and phagocytosis, tumor-derived signals, hypoxia, and nutrient deprivation reprogram these cells toward immunosuppressive phenotypes that promote tumor growth and immune evasion. This review, authored by researchers at Northwestern University's Feinberg School of Medicine, examines TAM-B-cell interactions and their role in glioblastoma immunosuppression. Key findings demonstrate extensive bidirectional communication between TAMs and B cells, wherein macrophages regulate B-cell activation and antigen presentation while B cells influence macrophage polarization. Metabolic competition within the tumor microenvironment—characterized by glucose depletion, lactate accumulation, and hypoxia—impairs B-cell functions and promotes regulatory B-cell development, reinforcing immune suppression. The article synthesizes findings on microbial metabolic reprogramming and macrophage-B-cell crosstalk, offering insights into potential therapeutic interventions targeting these immunometabolic mechanisms.

MimiVax and Roswell Park Comprehensive Cancer Center have released results from the SURVIVE Phase IIb clinical trial testing SurVaxM, a novel cancer vaccine designed to treat newly diagnosed glioblastoma. The trial enrolled 233 evaluable patients across 11 US cancer centers beginning in 2022. While SurVaxM failed to meet statistical significance as a primary endpoint across the entire patient population, improving median overall survival to 22.8 months compared to 20.3 months for placebo, the vaccine demonstrated statistically significant benefits in a prespecified subgroup of patients aged 65 and under, achieving median overall survival of 24.2 months versus 20.2 months. This younger cohort also showed significant improvement in progression-free survival, with 44 percent alive without progression at 12 months compared to 24 percent on placebo. Notably, approximately 42 percent of treated patients 65 and under survived 30 months or longer, representing a doubling of survival compared to placebo. SurVaxM is a first-in-class, patented peptide-mimic immunotherapeutic targeting survivin, a cell-survival protein present in approximately 95 percent of glioblastomas. Given the limited progress in glioblastoma treatment over two decades, these findings represent a meaningful advancement and provide a compelling case for FDA approval discussions.

This multicenter study evaluates whether patient-derived tumor organoid (PDO) drug sensitivity testing can guide treatment selection for adults with refractory, unresectable, or metastatic tumors. Fresh tumor tissue or malignant effusion is collected to establish PDOs, which undergo dose-response testing against clinically available drugs. Treatment decisions combine organoid sensitivity results with multidisciplinary clinical judgment, following guideline-recommended dosing protocols. Tumor response is assessed using RECIST version 1.1, with monitoring for progression, survival, and safety outcomes. The study encompasses nine tumor-specific cohorts, including non-small cell lung cancer, small cell lung cancer, prostate cancer, colorectal cancer, gastric cancer, pancreatic cancer, bladder cancer, pancreatic cancer, and non-clear cell renal cell carcinoma. Participants with failed organoid cultures or results exceeding 28 days are excluded from observation. This research addresses the critical clinical need for personalized treatment strategies in patients exhausting standard therapeutic options, potentially improving outcomes by matching drugs to individual tumor biology and sensitivity profiles.

Researchers at The Wistar Institute have developed a combination therapy that addresses two critical obstacles to immunotherapy success in glioblastoma, the most aggressive primary brain cancer in adults. Published in Neuro-Oncology, the study demonstrates that simultaneously reprogramming immunosuppressive myeloid cells while enhancing cancer-fighting T cells effectively shrinks tumors and prevents recurrence. While immunotherapy succeeds across many cancer types, glioblastoma response rates remain below ten percent. The research team, led by Dr. Filippo Veglia, identified that glioblastoma tumors exploit myeloid cells to suppress immune response while functional T cells become exhausted and ineffective. Through cell-by-cell analysis, scientists discovered that tumor hypoxia, or oxygen starvation, drives myeloid cell immunosuppression. Using axitinib, a low-dose drug already approved for kidney cancer treatment, the team relieved hypoxia within tumors, prevented myeloid reprogramming, and increased T cell infiltration. This dual-targeting approach represents a significant advance in making immunotherapy viable for glioblastoma patients, potentially transforming outcomes for this devastating disease.

Dendritic cell-based vaccines represent a promising immunotherapeutic approach for cancer treatment, yet their clinical efficacy remains inconsistent across malignancies. This narrative review synthesized evidence from human studies published between 2000 and 2026, examining dendritic cell vaccines in melanoma, glioblastoma, and prostate cancer through a comprehensive PubMed literature search using terms including "Sipuleucel-T" and "DCVax-L." While dendritic cell vaccines generally demonstrated safety and successfully activated tumor-specific T-cell responses, clinical outcomes proved heterogeneous. In melanoma, immune activation occurred frequently but with limited clinical benefit. DCVax-L improved overall survival in glioblastoma patients, whereas Sipuleucel-T provided modest survival benefits in prostate cancer. However, the phase III VIABLE trial testing DCVAC/PCa failed to improve overall survival. Engineered and biomaterial-based vaccine platforms showed immunogenicity but inconsistent efficacy. The findings suggest that despite eliciting antitumor immune responses, dendritic cell vaccines require optimization through combination therapeutic strategies to achieve clinically meaningful survival improvements and overcome tumor heterogeneity and immune evasion mechanisms.

Selective degradation of the endoplasmic reticulum (ER; reticulophagy) is a type of autophagy involved in the removal of ER fragments. So far, amino acid starvation as well as ER stress have been described as inducers of reticulophagy, which in turn restores cellular energy levels and ER homeostasis. Here, we explored the autophagy-inducing mechanisms that underlie the autophagic cell death (ACD)-triggering compound loperamide (LOP) in glioblastoma cells. Interestingly, LOP triggers upregulation of the transcription factor ATF4, which is accompanied by the induction of additional ER stress markers. Notably, knockout of ATF4 significantly attenuated LOP-induced autophagy and ACD. Functionally, LOP also specifically induces the engulfment of large ER fragments within autophagosomes and lysosomes as determined by electron and fluorescence microscopy. LOP-induced reticulophagy and cell death are predominantly mediated through the reticulophagy receptor RETREG1/FAM134B and, to a lesser extent, TEX264, confirming that reticulophagy receptors can promote ACD. Strikingly, apart from triggering LOP-induced autophagy and ACD, ATF4 is also required for LOP-induced reticulophagy. These observations highlight a key role for ATF4, RETREG1 and TEX264 in response to LOP-induced ER stress, reticulophagy and ACD, and establish a novel mechanistic link between ER stress and reticulophagy, with possible implications for additional models of drug-induced ER stress.

In cell culture, loperamide, a drug commonly used against diarrhea, proves effective against glioblastoma cells. A research team has now unraveled the drug's mechanisms of action of cell death induction and - in doing so - has shown how this compound could help attack brain tumors that otherwise are difficult to treat.

Oncolytic virotherapy represents a promising immunotherapeutic approach for cancer treatment that harnesses engineered or naturally occurring viruses to selectively destroy malignant cells while stimulating anti-tumor immune responses. This comprehensive review, published in October 2026 in Clinical and Experimental Medicine, examines the biological mechanisms underlying oncolytic virus function, including direct tumor cell lysis and immune system activation. The article synthesizes recent clinical advances demonstrating the efficacy of various oncolytic virus platforms in treating diverse cancer types, while addressing key challenges in optimizing viral delivery and overcoming tumor microenvironment barriers. The review discusses emerging strategies to enhance therapeutic potency through viral engineering and combination approaches with conventional therapies. By presenting current evidence and future research directions, this open-access publication provides clinicians and researchers with essential insights into the translational potential of oncolytic virotherapy, positioning it as an increasingly viable treatment modality within the evolving cancer care landscape alongside conventional chemotherapy and immunotherapy options.

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Glioblastoma multiforme remains one of oncology's most challenging malignancies, with median overall survival stubbornly hovering around fifteen months despite aggressive surgical resection, radiotherapy, and temozolomide chemotherapy. A comprehensive research perspective published in Oncoscience in September 2026 by Mamunur Rahman of East West University examines the evolving investigational landscape and concludes that the glioblastoma pipeline is undergoing fundamental transformation characterized by mechanistic breadth and biological sophistication. The article organizes emerging therapies into four mechanism-based domains: molecular-targeted therapies, immunotherapies and vaccines, oncolytic viruses and gene therapies, and agents targeting tumor metabolism and microenvironment. Critically, the field is shifting away from treating glioblastoma as a uniform disease toward biomarker-guided approaches that match treatments to individual tumor profiles. Patient selection increasingly relies on biomarkers including MGMT promoter methylation, IDH mutation status, EGFR amplification, and BRAF V600E alterations—defining biologically distinct patient groups. This stratification strategy mirrors successful paradigms established in lung cancer, breast cancer, and melanoma, offering renewed hope for improving outcomes in this historically refractory disease.

A phase III clinical trial published in JAMA Oncology in November 2022 demonstrated that DCVax-L, a dendritic-cell vaccine loaded with tumor lysate from patients' own glioblastoma tissue, significantly improved survival when added to standard treatment for this aggressive brain cancer. The study enrolled 232 newly diagnosed and 64 recurrent glioblastoma patients across four countries between 2007 and 2015, administering intradermal injections of 2.5 million dendritic cells on a schedule spanning from initial treatment through month 30, combined with conventional therapies including temozolomide, lomustine, or bevacizumab. Dendritic cells function as "professor cells" that educate the immune system by presenting tumor antigens to B and T lymphocytes, bridging innate and adaptive immunity. Survival outcomes were compared against external controls from 16 randomized trials involving over 2,000 patients. The treatment proved clinically and statistically superior to standard care alone in both newly diagnosed and recurrent cases, with manageable safety profiles—only five serious adverse events were potentially vaccine-related, including three cerebral edema cases and one infection. Notably, no autoimmune reactions or cytokine storms occurred. These findings support exploring dendritic-cell immunotherapy approaches earlier in glioblastoma treatment protocols.

Oncolytic virotherapy (OVT) represents a promising immunotherapy approach that kills cancer cells and triggers immunogenic cell death to activate anti-tumor immune responses. However, its effectiveness is limited in immunosuppressive "cold" solid tumors where the tumor microenvironment restricts viral infiltration and immune activation. This review examines how bacteriophages—safe, genetically manipulable bacterial viruses—can enhance OVT by leveraging their unique characteristics including repetitive peptide presentation, biological barrier degradation, and superior payload delivery capabilities. Two complementary approaches are proposed: the established synergistic method utilizing chimeric vectors like AAVP that combine phage safety and precision with oncolytic virus capabilities, and a modular approach transferring specific bacteriophage traits to replication-competent oncolytic viruses. Notably, researchers have used artificial intelligence and genetic engineering to create the first mammalian-encoded hyaluronate lyase, a synthetically produced variant that avoids tumor-promoting effects of existing mammalian extracellular matrix-degrading enzymes. This innovation is timely given cancer's devastating global impact, with WHO reporting 10 million deaths in 2022 and projections reaching 18.5 million deaths by 2050, underscoring urgent demand for effective immunotherapeutic strategies.

Vacunas is the official journal of the Asociación Española de Vacunología, dedicated to publishing research on vaccine-preventable diseases in humans and animals with zoonotic potential. The journal emphasizes planning and evaluation aspects, including epidemiology of immunopreventable diseases, vaccination program development, and assessment of vaccination efficacy, effectiveness, and efficiency. Accepting submissions in both Spanish and English, Vacunas covers diverse areas including vaccine development and evaluation, regulatory affairs, vaccine technology encompassing vectors and adjuvants, public health policies, vaccine immunology and mechanisms of action, safety and effectiveness assessment, and vaccine acceptance. Notably, the journal extends its scope to vaccines for chronic conditions, autoimmune diseases, allergies, and non-communicable diseases, reflecting contemporary medical challenges. Additionally, it addresses veterinary vaccines for animal health through a One Health perspective, recognizing the interconnection between human and animal health systems. This comprehensive editorial focus positions Vacunas as a significant platform for advancing vaccine science and public health knowledge across multiple disciplines and disease categories.

A comprehensive research perspective published in Oncoscience examines the evolving glioblastoma multiforme (GBM) treatment landscape for 2025–2026, highlighting unprecedented mechanistic diversity in the investigational pipeline. Led by Mamunur Rahman from East West University in Bangladesh, the review organizes emerging therapies into four major categories: molecular-targeted therapies, immunotherapies and vaccines, oncolytic viruses and gene therapies, and agents targeting tumor metabolism and microenvironment. GBM remains lethal despite standard treatment with surgery, radiotherapy and temozolomide, with median overall survival around 15 months. The article addresses formidable biological barriers including genetic tumor heterogeneity, immunosuppressive microenvironments, blood-brain barrier penetration challenges, and hypoxia-driven resistance. Key molecularly targeted approaches discussed include CDK4/6 inhibitors like abemaciclib combined with ERK inhibitor LY3214996, and regorafenib, which demonstrated improved survival versus lomustine in the Phase 2 REGOMA trial for recurrent GBM. The review emphasizes biomarker-guided patient selection, leveraging MGMT promoter methylation, IDH mutations, EGFR amplification and BRAF V600E status to identify biologically distinct patient subgroups for optimized treatment strategies.

Glioblastoma remains a highly aggressive and treatment-resistant primary brain malignancy with limited long-term survival improvements despite multimodal therapeutic advances. Glioblastoma stem cells (GSCs) drive tumor initiation, recurrence, and therapeutic resistance through complex interactions with the tumor immune microenvironment (TIME). This comprehensive review examines the molecular and cellular mechanisms of GSC-TIME crosstalk, focusing on key immune populations including tumor-associated macrophages, myeloid-derived suppressor cells, T cells, regulatory T cells, natural killer cells, and neutrophils. Critical signaling pathways are identified, including B2M/TGF-β1, IL8/CXCR2, IFI35/NF-κB, lactate/lactylation, and m6A/LOXL2, alongside extracellular vesicle-mediated communication. These interactions sustain GSC stemness, enable metabolic adaptation, facilitate immune escape, and confer resistance to radiotherapy, temozolomide, and targeted therapies. The review evaluates emerging therapeutic strategies including TAM/MDSC reprogramming, metabolic and epigenetic interventions, immune checkpoint blockade, bispecific antibodies, CAR-T/NK cell therapy, and extracellular vesicle-based delivery. Understanding GSC-TIME crosstalk is essential for developing precision therapies that address the spatial heterogeneity and blood-brain barrier challenges inherent to glioblastoma treatment.

T-cell immunotherapies have revolutionized treatment for blood cancers but show limited effectiveness against solid tumors, primarily due to restrictive tumor microenvironments that impede immune-cell trafficking and function. Researchers employed advanced techniques including dynamic imaging of human tumor tissue, multiparametric cytometry, single-cell transcriptomics, and spatial analysis to identify specific barriers to T-cell infiltration. Their findings reveal that extracellular-matrix architecture physically constrains T-cell movement, tumor-associated macrophages create additional blockades to T-cell entry, and mitochondrial metabolism is critical for CD8 T-cell motility and infiltration efficiency. This work now extends to CAR-T cell development for adult and pediatric solid tumors through the Cancer Grand Challenges NexTGen program. By correlating CAR-T-cell behavior and activation with tumor microenvironment composition, researchers aim to discover predictive biomarkers for treatment response and develop rational combination strategies that enhance infiltration and anti-tumor effectiveness. These human ex vivo models bridge mechanistic immunology with clinical application, potentially accelerating development of improved cellular therapies for solid cancers.

This research topic examines how immunosuppression in solid tumors emerges from complex interactions between tumor cells, immune cells, and stromal cells within distinct microenvironmental contexts. Rather than being driven by single mechanisms, immunosuppression is shaped by both spatial organization and metabolic conditions affecting populations such as regulatory T cells, tumor-associated macrophages, and cancer-associated fibroblasts. The collection comprises nine original research articles and four reviews analyzing immunosuppression across multiple biological scales. Key findings reveal that COL11A1-positive cancer-associated fibroblasts accumulate at tumor boundaries, correlating with reduced cytotoxic T cell and B cell activation. Multiplex immunofluorescence studies in non-small cell lung cancer identified BAG3-positive fibroblasts spatially associated with CD8 T cells as markers of neoadjuvant chemoimmunotherapy resistance. Research also demonstrates that molecules like MUC16 inhibit natural killer cell immune synapse formation with cancer cells. Understanding these spatial and metabolic dimensions is critical for developing more effective immunotherapy strategies targeting the tumor microenvironment's multiscale architecture.

Scientists from the German Cancer Research Center (DKFZ) and ShanghaiTech University have developed an innovative method for growing brain tumors of individual patients in the laboratory that mimic the original structure and the molecular property of the parental tumor as closely as possible. Drug tests in this model were found to correlate very well with actual patient responses, making it a valuable method for investigating therapies.

A personalized vaccine to treat glioblastoma, a fast-growing and incurable brain cancer that affects four in 100,000 people in the U.S., is safe and elicits robust and broad immune responses that appears to increase recurrence-free survival in a subset of patients after surgery, according to an early-stage clinical trial co-led by researchers at Washington University School of Medicine in St. Louis.

UC San Diego is conducting multiple clinical trials in 2026 targeting glioblastoma and related brain cancers, enrolling eligible patients aged 18 and older. The first phase I/II trial investigates selinexor, a selective inhibitor of nuclear export (SINE) that blocks the CRM1 protein to impede cancer cell growth, administered alongside standard temozolomide chemotherapy in recurrent glioblastoma patients. A second phase I trial tests triapine, which inhibits enzymes necessary for tumor cell growth, combined with radiation therapy for recurrent glioblastoma and astrocytoma. The third multicenter study evaluates DB107-RRV and DB107-FC (formerly Toca 511 and Toca FC) following surgical resection in newly diagnosed high-grade glioma patients, comparing outcomes to historical control data when added to standard care including radiation and temozolomide using the Stupp Protocol. These trials matter because glioblastoma remains a devastating diagnosis with limited treatment options; combination approaches targeting different molecular pathways may improve survival and progression-free survival rates for both newly diagnosed and recurrent cases.