glioblastoma immunotherapy

BACKGROUND: GBM, also known as glioblastoma multiforme, is the most prevalent and lethal type of brain cancer. The cell proliferation, invasion, angiogenesis, and treatment of gliomas are significantly influenced by oxidative stress. Nevertheless, the connection between ORGs and GBM remains poorly comprehended. The objective of this research is to investigate the predictive significance of ORGs in GBM and their potential as targets for therapy. METHODS: We identified differentially expressed genes in glioma and ORGs from public databases...

BACKGROUND: Glioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Current treatment options are limited and often ineffective. CAR T cell therapy has shown success in treating hematologic malignancies, and there is growing interest in its potential application in solid tumors, including GBM. However, current CAR T therapy lacks clinical efficacy against GBM due to tumor-related resistance mechanisms and CAR T cell deficiencies. Therefore, there is a need to improve CAR T cell therapy efficacy in GBM...

Mounting evidence is identifying human cytomegalovirus (HCMV) as a potential oncogenic virus. HCMV has been detected in glioblastoma multiforme (GB). Herewith, we present the first experimental evidence for the generation of CMV-Elicited Glioblastoma Cells (CEGBCs) possessing glioblastoma-like traits that lead to the formation of glioblastoma in orthotopically xenografted mice. In addition to the already reported oncogenic HCMV-DB strain, we isolated three HCMV clinical strains from GB tissues that transformed HAs toward CEGBCs and generated spheroids from CEGBCs that resulted in the appearance of glioblastoma-like tumors in xenografted mice...

Glioblastoma (GBM) remains an orphan cancer disease with poor outcome. Novel treatment strategies are needed. Immunotherapy has several modes of action. The addition of active specific immunotherapy with dendritic cell vaccines resulted in improved overall survival of patients. Integration of DC vaccination within the first-line combined treatment became a challenge, and immunogenic cell death immunotherapy during chemotherapy was introduced. We used a retrospective analysis using real world data to evaluate the complex combined treatment, which included individualized multimodal immunotherapy during and after standard of care, and which required adaptations during treatment, and found a further improvement of overall survival...

Glioblastoma (GBM) is the deadliest of all brain cancers. GBM patients receive an intensive treatment schedule consisting of surgery, radiotherapy and chemotherapy, which only modestly extends patient survival. Therefore, preclinical studies are testing novel experimental treatments. In such preclinical studies, these treatments are administered as monotherapy in the majority of cases; conversely, in patients the new treatments are always combined with the standard of care. Most likely, this difference contributes to the failure of clinical trials despite the successes of the preclinical studies...

The discovery of the concept of immunogenic cell death (ICD) is a cornerstone in the development of novel anti-cancer immunotherapeutic approaches. Induction of the ICD pathway by specific anti-cancer therapeutic regimens can eliminate cancer cells by directly killing them during therapy and by activation of strong and specific anti-cancer immunity, leading to a long-lasting immunological memory that prevents cancer recurrence. ICD encompasses different forms of regulated cell death and can be triggered by many anti-cancer treatment modalities, including photodynamic therapy (PDT)...

Dendritic cell vaccination is a form of active immunotherapy that aims to exploit the crucial role of DC in the initiation of T-cell responses. Numerous vaccination trials have been conducted targeting various tumor entities, including glioblastoma, the most frequent and aggressive malignant brain tumor in adults. They have demonstrated feasibility and safety and suggest improved survival, associated with induction of anti-tumoral immunity. Here, we describe in detail a large-scale 2-step protocol for successive GMP-compliant generation of immature and mature dendritic cells, yielding a highly homogenous population of CD83+ mature DC expressing CD40, CD80, CD86 and HLA-DR at high density, lacking activity of the immunosuppressive enzyme indoleamine-2,3-dioxygenase, migrating towards the chemokine CCL19 and showing highly potent T-cell stimulatory activity...

PURPOSE OF REVIEW: The purpose of this review is to discuss a wide variety of novel therapies recently studied or actively undergoing study in patients with glioblastoma. This review also discusses current and future strategies for improving clinical trial design in patients with glioblastoma to maximize efficacy in discovering effective treatments. RECENT FINDINGS: Over the years, there has been significant expansion in therapy modalities studied in patients with glioblastoma...

Various types of brain tumors occur in both children and adults. These tumors manifest with different characteristics such as malignancy, cellular lineage, location of origin, and genomic profile. Recently, immunotherapy, which manipulates immune cells in the tumor microenvironment (TME) to kill tumor cells, has attracted attention as a treatment strategy for tumors. Here, we analyzed the transcriptomic architecture of the brain tumor microenvironment to provide potential guidelines to overcome the therapeutic vulnerabilities to brain tumors...

BACKGROUND: World Health Organization (WHO) grade 4 adult-type diffuse glioma is the most malignant primary tumor of the brain. Nucleolar protein 14 ( NOP14 ) is recognized to contribute significantly to the assembly of small ribosomal subunits. However, the specific involvement of NOP14 in diverse cancers remains poorly understood, particularly its role in adult-type diffuse glioma, which has yet to be elucidated. METHODS: A total of 20 adult-type diffuse glioma samples with varying WHO stages were collected...

We found that immunosuppressive monocytic-myeloid-derived suppressor cells (M-MDSCs) were more likely to be recruited by glioblastoma (GBM) through adhesion molecules on GBM-associated endothelial cells upregulated post-chemoradiotherapy. These cells are continuously generated during tumor progression, entering tumors and expressing PD-L1 at a high level, allowing GBM to exhaust T cells and evade attack from the immune system, thereby facilitating GBM relapse. αLy-6C-LAMP is composed of (i) drug cores with slightly negative charges condensed by cationic protamine and plasmids encoding PD-L1 trap protein, (ii) pre-formulated cationic liposomes targeted to Ly-6C for encapsulating the drug cores, and (iii) a layer of red blood cell membrane on the surface for effectuating long-circulation...

Glioblastoma is the most prevalent and fatal form of primary brain tumors. New targeted therapeutic strategies for this type of tumor are imperative given the dire prognosis for glioblastoma patients and the poor results of current multimodal therapy. Previously reported drawbacks of antibody-based therapeutics include the inability to translocate across the blood-brain barrier and reach intracellular targets due to their molecular weight. These disadvantages translate into poor target neutralization and cancer maintenance...

Despite enormous efforts being invested in the development of novel therapies for brain malignancies, there remains a dire need for effective treatments, particularly for pediatric glioblastomas. Their poor prognosis has been attributed to the fact that conventional therapies target tumoral cells, but not glioblastoma stem cells (GSCs). GSCs are characterized by self-renewal, tumorigenicity, poor differentiation, and resistance to therapy. These characteristics represent the fundamental tools needed to recapitulate the tumor and result in a relapse...

Pediatric high-grade glioma (pHGG) including pediatric glioblastoma (pGBM) are highly aggressive pediatric central nervous system (CNS) malignancies. pGBM comprises approximately 3% of all pediatric CNS malignancies and has a 5-year survival rate of approximately 20%. Surgical resection and chemoradiation are often the standard of care for pGBM and pHGG, however, even with these interventions, survival for children diagnosed with pGBM and pHGG remains poor. Due to shortcomings associated with the standard of care, many efforts have been made to create novel immunotherapeutic approaches targeted to these malignancies...

BACKGROUND: Cancer represents a widespread global health challenge impacting millions of individuals worldwide. Identifying new targets for cancer treatment is a crucial step in developing more effective therapies. Among these potential targets, Coactosin-like protein 1 (COTL1), a cytoskeleton-associated protein with critical roles in cell migration, adhesion, and signaling, has shown involvement in tumor progression. METHODS: GSCA, TIMER, SangerBox database were used to explore the COTL1 expression across different tumor types...

Glioblastoma (GB) is an intrusive and recurrent primary brain tumor with low survivability. The heterogeneity of the tumor microenvironment plays a crucial role in the stemness and proliferation of GB. The tumor microenvironment induces tumor heterogeneity of cancer cells by facilitating clonal evolution and promoting multidrug resistance, leading to cancer cell progression and metastasis. It also plays an important role in angiogenesis to nourish the hypoxic tumor environment. There is a strong interaction of neoplastic cells with their surrounding microenvironment that comprise several immune and non-immune cellular components...

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Glioblastoma multiform (GBM) is the most prevalent CNS (central nervous system) tumor in adults, with an average survival length shorter than 2 years and rare metastasis to organs other than CNS. Despite extensive attempts at surgical resecting, the inherently permeable nature of this disease has rendered relapse nearly unavoidable. Thus, immunotherapy is a feasible alternative, as stimulated immune cells can enter into the remote and inaccessible tumor cells. Immunotherapy has revolutionized patient upshots in various malignancies and might introduce different effective ways for GBM patients...

Glioblastoma multiforme (GBM) is the most aggressive brain cancer, characterized by a rapid and drug-resistant progression. GBM "builds" around its primary core a genetically heterogeneous tumor-microenvironment (TME), recruiting surrounding healthy brain cells by releasing various intercellular signals. Glioma-associated microglia (GAM) represent the largest population of collaborating cells, which, in the TME, usually exhibit the anti-inflammatory M2 phenotype, thus promoting an immunosuppressing environment that helps tumor growth...

In cancer immunotherapy, chimeric antigen receptors (CARs) targeting specific antigens have become a powerful tool for cell-based therapy. CAR-natural killer (NK) cells offer selective anticancer lysis with reduced off-tumor toxicity compared to CAR-T cells, which is beneficial in the heterogeneous milieu of solid tumors. In the tumor microenvironment (TME) of glioblastoma (GBM), pericytes not only support tumor growth but also contribute to immune evasion, underscoring their potential as therapeutic targets in GBM treatment...