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Neuro-oncology Jul 2014Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and... (Review)
Review
Gliomas are the most common primary intracranial tumor, representing 81% of malignant brain tumors. Although relatively rare, they cause significant mortality and morbidity. Glioblastoma, the most common glioma histology (∼45% of all gliomas), has a 5-year relative survival of ∼5%. A small portion of these tumors are caused by Mendelian disorders, including neurofibromatosis, tuberous sclerosis, and Li-Fraumeni syndrome. Genomic analyses of glioma have also produced new evidence about risk and prognosis. Recently discovered biomarkers that indicate improved survival include O⁶-methylguanine-DNA methyltransferase methylation, isocitrate dehydrogenase mutation, and a glioma cytosine-phosphate-guanine island methylator phenotype. Genome-wide association studies have identified heritable risk alleles within 7 genes that are associated with increased risk of glioma. Many risk factors have been examined as potential contributors to glioma risk. Most significantly, these include an increase in risk by exposure to ionizing radiation and a decrease in risk by history of allergies or atopic disease(s). The potential influence of occupational exposures and cellular phones has also been examined, with inconclusive results. We provide a “state of the science” review of current research into causes and risk factors for gliomas in adults.
Topics: Adult; Brain Neoplasms; Glioma; Humans; Risk Factors
PubMed: 24842956
DOI: 10.1093/neuonc/nou087 -
Frontiers in Immunology 2022In cancer, neutrophils are an important part of the tumour microenvironment (TME). Previous studies have shown that circulating and infiltrating neutrophils are... (Review)
Review
In cancer, neutrophils are an important part of the tumour microenvironment (TME). Previous studies have shown that circulating and infiltrating neutrophils are associated with malignant progression and immunosuppression in gliomas. However, recent studies have shown that neutrophils have an antitumour effect. In this review, we focus on the functional roles of neutrophils in the circulation and tumour sites in patients with glioma. The mechanisms of neutrophil recruitment, immunosuppression and the differentiation of neutrophils are discussed. Finally, the potential of neutrophils as clinical biomarkers and therapeutic targets is highlighted. This review can help us gain a deeper and systematic understanding of the role of neutrophils, and provide new insights for treatment in gliomas.
Topics: Glioma; Humans; Immunosuppression Therapy; Neutrophil Infiltration; Neutrophils; Tumor Microenvironment
PubMed: 35860278
DOI: 10.3389/fimmu.2022.927233 -
Frontiers in Immunology 2023Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being the most common and aggressive type. Despite two decades of... (Review)
Review
Gliomas are the most prevalent primary malignant brain tumors worldwide, with glioblastoma (GBM) being the most common and aggressive type. Despite two decades of relentless pursuit in exploring novel therapeutic approaches for GBM, there is limited progress in improving patients' survival outcomes. Numerous obstacles impede the effective treatment of GBM, including the immunosuppressive tumor microenvironment (TME), the blood-brain barrier, and extensive heterogeneity. Despite these challenges, immunotherapies are emerging as a promising avenue that may offer new hope for the treatment of gliomas. There are four main types of immunotherapies for gliomas, immune checkpoint blockades, chimeric antigen receptor T-cell therapies, vaccines, and oncolytic viruses. In addition, gene therapy, bispecific antibody therapy, and combine therapy are also briefly introduced in this review. The significant role of TME in the process of immunotherapies has been emphasized in many studies. Although immunotherapy is a promising treatment for gliomas, enormous effort is required to overcome the existing barriers to its success. Owing to the rapid development and increasing attention paid to immunotherapies for gliomas, this article aims to review the recent advances in immunotherapies for gliomas.
Topics: Humans; Immunotherapy; Glioma; Glioblastoma; Immunotherapy, Adoptive; Radioimmunotherapy; Tumor Microenvironment
PubMed: 37744349
DOI: 10.3389/fimmu.2023.1255611 -
Signal Transduction and Targeted Therapy Nov 2023Glioma is the most prevalent brain tumor, presenting with limited treatment options, while patients with malignant glioma and glioblastoma (GBM) have poor prognoses. The...
Glioma is the most prevalent brain tumor, presenting with limited treatment options, while patients with malignant glioma and glioblastoma (GBM) have poor prognoses. The physical obstacle to drug delivery imposed by the blood‒brain barrier (BBB) and glioma stem cells (GSCs), which are widely recognized as crucial elements contributing to the unsatisfactory clinical outcomes. In this study, we found a small molecule, gambogic amide (GA-amide), exhibited the ability to effectively penetrate the blood-brain barrier (BBB) and displayed a notable enrichment within the tumor region. Moreover, GA-amide exhibited significant efficacy in inhibiting tumor growth across various in vivo glioma models, encompassing transgenic and primary patient-derived xenograft (PDX) models. We further performed a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) knockout screen to determine the druggable target of GA-amide. By the combination of the cellular thermal shift assay (CETSA), the drug affinity responsive target stability (DARTS) approach, molecular docking simulation and surface plasmon resonance (SPR) analysis, WD repeat domain 1 (WDR1) was identified as the direct binding target of GA-amide. Through direct interaction with WDR1, GA-amide promoted the formation of a complex involving WDR1, MYH9 and Cofilin, which accelerate the depolymerization of F-actin to inhibit the invasion of patient-derived glioma cells (PDCs) and induce PDC apoptosis via the mitochondrial apoptotic pathway. In conclusion, our study not only identified GA-amide as an effective and safe agent for treating glioma but also shed light on the underlying mechanisms of GA-amide from the perspective of cytoskeletal homeostasis.
Topics: Humans; Molecular Docking Simulation; Cell Line, Tumor; Glioma; Cytoskeleton; Amides; Microfilament Proteins
PubMed: 37935665
DOI: 10.1038/s41392-023-01666-3 -
Current Treatment Options in Oncology Jul 2020Malignant gliomas remain a challenging cancer to treat due to limitations in both therapeutic and efficacious options. Tumor treating fields (TTFields) have emerged as a... (Review)
Review
Malignant gliomas remain a challenging cancer to treat due to limitations in both therapeutic and efficacious options. Tumor treating fields (TTFields) have emerged as a novel, locoregional, antineoplastic treatment modality with favorable efficacy and safety being demonstrated in the most aggressive type of malignant gliomas, glioblastoma (GBM). In 2 large randomized, controlled phase 3 trials, the addition of TTFields was associated with increased overall survival when combined with adjuvant temozolomide (TMZ) chemotherapy in patients with newly diagnosed GBM (ndGBM) and comparable overall survival compared with standard chemotherapy in patients with recurrent GBM (rGBM). TTFields target cancer cells by several mechanisms of action (MoA) including suppression of proliferation, migration and invasion, disruption of DNA repair and angiogenesis, antimitotic effects, and induction of apoptosis and immunogenic cell death. Having several MoAs makes TTFields an attractive modality to combine with standard, salvage, and novel treatment regimens (e.g., radiotherapy, chemotherapy, and immunotherapy). Treatment within the field of malignant gliomas is evolving to emphasize combinatorial approaches that work synergistically to improve patient outcomes. Here, we review the current use of TTFields in GBM, discuss MOA and treatment delivery, and consider the potential for its wider adoption in other gliomas.
Topics: Algorithms; Brain Neoplasms; Clinical Decision-Making; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Factor Analysis, Statistical; Glioblastoma; Glioma; Humans; Radiofrequency Ablation; Treatment Outcome
PubMed: 32734509
DOI: 10.1007/s11864-020-00773-5 -
Strahlentherapie Und Onkologie : Organ... Oct 2020Magnetic resonance imaging (MRI) and amino acid positron-emission tomography (PET) of the brain contain a vast amount of structural and functional information that can... (Review)
Review
BACKGROUND
Magnetic resonance imaging (MRI) and amino acid positron-emission tomography (PET) of the brain contain a vast amount of structural and functional information that can be analyzed by machine learning algorithms and radiomics for the use of radiotherapy in patients with malignant brain tumors.
METHODS
This study is based on comprehensive literature research on machine learning and radiomics analyses in neuroimaging and their potential application for radiotherapy in patients with malignant glioma or brain metastases.
RESULTS
Feature-based radiomics and deep learning-based machine learning methods can be used to improve brain tumor diagnostics and automate various steps of radiotherapy planning. In glioma patients, important applications are the determination of WHO grade and molecular markers for integrated diagnosis in patients not eligible for biopsy or resection, automatic image segmentation for target volume planning, prediction of the location of tumor recurrence, and differentiation of pseudoprogression from actual tumor progression. In patients with brain metastases, radiomics is applied for additional detection of smaller brain metastases, accurate segmentation of multiple larger metastases, prediction of local response after radiosurgery, and differentiation of radiation injury from local brain metastasis relapse. Importantly, high diagnostic accuracies of 80-90% can be achieved by most approaches, despite a large variety in terms of applied imaging techniques and computational methods.
CONCLUSION
Clinical application of automated image analyses based on radiomics and artificial intelligence has a great potential for improving radiotherapy in patients with malignant brain tumors. However, a common problem associated with these techniques is the large variability and the lack of standardization of the methods applied.
Topics: Brain Neoplasms; Computational Biology; DNA Methylation; DNA Modification Methylases; DNA Repair Enzymes; Deep Learning; Diagnosis, Differential; Glioblastoma; Glioma; Humans; Image Processing, Computer-Assisted; Imaging Genomics; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Neoplasm Grading; Neoplasm Proteins; Neoplasm Recurrence, Local; Neuroimaging; Positron-Emission Tomography; Progression-Free Survival; Promoter Regions, Genetic; Radiation Oncology; Radiosurgery; Radiotherapy Planning, Computer-Assisted; Sensitivity and Specificity; Tumor Suppressor Proteins
PubMed: 32394100
DOI: 10.1007/s00066-020-01626-8 -
Aging Sep 2021
Topics: Antineoplastic Agents; Brain Neoplasms; CX3C Chemokine Receptor 1; Gene Expression Regulation, Neoplastic; Glioma; Humans
PubMed: 34516407
DOI: 10.18632/aging.203536 -
CNS Neuroscience & Therapeutics Nov 2023Tumor-associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the...
AIMS
Tumor-associated macrophages (TAMs) in the immune microenvironment play an important role in the increased drug resistance and recurrence of malignant glioma, but the mechanism remains incompletely inventoried. The focus of this study was to investigate the distinctions of M2-like TAMs in the immune microenvironment between primary and recurrent malignant glioma and its influence in the recurrence.
METHODS
We employed single-cell RNA sequencing to construct a single-cell atlas for a total of 23,010 individual cells from 6 patients with primary or recurrent malignant glioma and identified 5 cell types, including TAMs and malignant cells. Immunohistochemical techniques and proteomics analysis were performed to investigate the role of intercellular interaction between malignant cells and TAMs in the recurrence of malignant glioma.
RESULTS
Six subgroups of TAMs were annotated and M2-like TAMs were found to increase in recurrent malignant glioma significantly. A pseudotime trajectory and a dynamic gene expression profiling during the recurrence of malignant glioma were reconstructed. Up-regulation of several cancer pathways and intercellular interaction-related genes are associated with the recurrence of malignant glioma. Moreover, the M2-like TAMs can activate the PI3K/Akt/HIF-1α/CA9 pathway in the malignant glioma cells via SPP1-CD44-mediated intercellular interaction. Interestingly, high expression of CA9 can trigger the immunosuppressive response in the malignant glioma, thus promoting the degree of malignancy and drug resistance.
CONCLUSION
Our study uncovers the distinction of M2-like TAMs between primary and recurrent glioma, which offers unparalleled insights into the immune microenvironment of primary and recurrent malignant glioma.
Topics: Humans; Proteomics; Phosphatidylinositol 3-Kinases; Single-Cell Gene Expression Analysis; Neoplasm Recurrence, Local; Macrophages; Glioma; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37194413
DOI: 10.1111/cns.14269 -
Cancer Gene Therapy May 2023Glioma is the most common primary central nervous system tumor in adults. Aquaporin-4, as a water channel protein encoded by AQP4 in the brain, is reported to alter its...
Glioma is the most common primary central nervous system tumor in adults. Aquaporin-4, as a water channel protein encoded by AQP4 in the brain, is reported to alter its aggregation status to affect plasma membrane dynamics and provide the potential for metastasis of tumor cells and components of the tumor microenvironment. We performed single-cell RNA transcriptome sequencing of 53059 cells from 13 malignant glioma samples and spotted that the expression of AQP4 differed between samples. The same result was observed in the TCGA glioma database, showing poor overall survival and poor response to chemotherapy in AQP4 overexpressed populations. Concomitant with the overexpression of AQP4, genes related to the immune system were also over-expressed, such as CD74, HES1, CALD1, and HEBP2, indicating AQP4 may relate to immune factors of tumor progression. We also found that tumor-associated macrophages tended to polarize toward M2 macrophages in the high AQP4 group. In glioblastoma samples, we examined cell status differences and identified that cell status differs according to AQP4 expression levels. Briefly, our study revealed substantial heterogeneity within malignant gliomas with different AQP4 expression levels, indicating the intricate connection between tumor cells and the tumor immune environment.
Topics: Humans; Adult; Glioma; Brain Neoplasms; Glioblastoma; Macrophages; Sequence Analysis, RNA; Tumor Microenvironment; Heme-Binding Proteins; Pregnancy Proteins
PubMed: 36599974
DOI: 10.1038/s41417-022-00582-y -
Frontiers in Immunology 2022Lower-grade glioma (LGG) is a common malignant primary tumour in the central nervous system, and most patients eventually develop highly aggressive gliomas despite...
Lower-grade glioma (LGG) is a common malignant primary tumour in the central nervous system, and most patients eventually develop highly aggressive gliomas despite comprehensive traditional treatment. Tumour molecular subtypes and prognostic biomarkers play a crucial role in LGG diagnosis and treatment. Therefore, the identification of novel biomarkers in LGG patients is crucial for predicting the prognosis of glioma. Immunogenic cell death (ICD) is defined as regulated cell death that is sufficient to activate the adaptive immune response of immunocompetent hosts. The combination of ICD and immunotherapy might exert a greater and more persistent antitumour effect in gliomas. In our study, we explored the expression, function, and genetic alterations of 34 ICD-related genes. Using 12 ICD-related genes, including IL17RA, IL1R1, EIF2AK3, CD4, PRF1, CXCR3, CD8A, BAX, PDIA3, CASP8, MYD88, and CASP1, we constructed and validated an ICD-related risk signature least absolute shrinkage and selection operator (LASSO) Cox regression analysis. All the information was obtained from public databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and the Chinese Glioma Genome Atlas (CGGA) databases. Our results revealed that ICD-high risk groups have a poor prognosis and might be more sensitive to immune checkpoint blockade (ICB) immunotherapy. In addition, ICD-high risk groups were associated with 1p19q noncodeletion, higher WHO grade, wild type IDH, and an immunosuppressive tumour microenvironment. We verified the prognostic value of 12 ICD-related genes in TCGA and CGGA databases. Immunohistochemistry was performed to verify the expression of several ICD-related genes at the protein level. Our study provides a novel and comprehensive perspective to elucidate the underlying mechanisms of LGG prognosis and direction for future individualized cancer immunotherapy.
Topics: Humans; Brain Neoplasms; Tumor Microenvironment; Immunogenic Cell Death; Transcriptome; Glioma; Prognosis
PubMed: 36325335
DOI: 10.3389/fimmu.2022.1011757