Glioblastoma: two immune subtypes under the surface of the cold tumor

Xiong, Wu; Cong, Li; Kong, Guang; Wan, Bowen; Wang, Siming; Fan, Jin

doi:10.18632/aging.204067

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…One of the many reasons is the glioma immunosuppressive tumor microenvironment (TME) (Quail and Joyce 2017 ). As previously reported, the TME of glioma is immunosuppressive and is known as one of the cold immune tumors (D'Alessio, et al 2019 ; Xiong et al 2022 ). More key molecules need to be identified to understand the TME of glioma and improve the outcomes of glioma patients.…”

Section: Introductionmentioning

confidence: 79%

Cuproptosis-related gene SLC31A1 expression correlates with the prognosis and tumor immune microenvironment in glioma

Wang,

Li,

Guo

et al. 2023

Funct Integr Genomics

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Cuproptosis is a newly discovered form of cell death. It is regulated by a string of genes. The genes are identified to influence the tumor progression, but in glioma, the cuproptosis-related genes are little studied. The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) were used to screen for SLC31A1 gene expression in glioma and healthy tissue samples. The results were validated using the Gene Expression Omnibus (GEO) and quantitative real-time polymerase chain reaction (qPCR). The Human Protein Atlas (HPA) and the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) were used to validate our results at the protein level. Multivariable analysis and Kaplan–Meier survival curves were used to examine the relationship among SLC31A1 gene expression, clinical parameters, and survival rates. The online Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to find the genes and proteins that correlate to SLC31A1. The immune infiltration analysis was performed using the Tumor Immune Estimation Resource (TIMER) databases. Small interfering RNA was used to knock down the SLC31A1 expression, and the cell proliferation, apoptosis, and migration were analyzed using cell counting kit-8, flow cytometry, and transwell. The glioma patients have higher SLC31A1 expression levels, which increase as the World Health Organization (WHO) grade escalates. The survival analysis illustrates that the SLC31A1 gene expression negatively correlates with overall survival (OS), progression-free survival (PFS), and disease-specific survival (DSS). The immune infiltration analysis shows the SLC31A1 gene positively correlates with T helper 2 (Th2) cells, macrophages, and M2-type macrophages and negatively correlates with plasmacytoid dendritic cells (pDCs), natural killer (NK) CD56bright cells, and CD8 T cells. The in vitro KD experiment shows the SLC31A1 knockdown depressed the glioma cell proliferation and migration and promoted the apoptosis rate. The SLC31A1 gene expression can shorten the survival time of glioma patients. In vitro study shows that SLC31A1 can promote cell proliferation, and migration, and depress the cell apoptosis of glioma cells. It also can promote the formation of a tumor-suppressive microenvironment.

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Section: Introductionmentioning

confidence: 79%

Cuproptosis-related gene SLC31A1 expression correlates with the prognosis and tumor immune microenvironment in glioma

Wang,

Li,

Guo

et al. 2023

Funct Integr Genomics

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“…According to some studies, enolase is a critical element in adaptation to cellular stress and (inter) acts with cathepsins (cathepsins cleave the C-terminal dipeptide of γ-enolase). It thus may have an undening role in tumor immunology making a bridge between GBM metabolism and immunology pathways [34]. In consequence, this immunometabolic pro le of GBM is supported by immunosupressive tumor microenvironment and is additionally regulated by altered tumor metabolism, creating an immunologically ,,cold tumor''.…”

Section: Discussionmentioning

confidence: 99%

Cancer- related protein profile of patient-derived and commercial glioblastoma cell lines exposed to Temozolomide

Wajdman

Machnik

Linnebacher

et al. 2023

Preprint

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Purpose Since recurrence is observed in almost all glioma patients deeper insight into mechanisms responsible for therapy resistance and identification of new biomarkers is urgently required. In this study were analyzed differences in expression of 84 cancer- related proteins in three GBM cell lines: the commercial T98G cells and two patient-derived cell lines. Materials and Methods Influence of temozolomide (TMZ) on changes in proteins expression, cell morphology and migration was investigated. Analyzed lines were characterized by different remarkable plasticity of proteins expression and proteomic alterations induced by TMZ. Among 10 proteins expressed in all lines, 5 (Cathepsin b, FGF, Survivin, AXL, Osteopontin) were modulated by TMZ administration. Results As a result of TMZ exposition in both HROG02 and T98G cell lines proteins involved in chemoresistance and invasion (TIE-2, Thrombospondin) were detected. This suggests that TMZ promoted their malignant phenotype even further. In control culture (not subjected to TMZ) of HROG17 cells proteins involved in metabolism were strongly suppressed. Conclusion The presented data shed a new light on the immunometabolic profile of glioma proteome and its plasticity in response to Temozolomide interventions. Cathepsin b, FGF, Survivin, AXL and Osteopontin seem to be promising targets for a multimodal treatment that could be applied to inhibit GBM recurrence in the future.

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“…Immunotherapy strategies targeting the Gb tumor microenvironment have become the focus of Gb treatment options, and TAM-targeted therapy has great potential in glioma treatment strategies ( 13 ). In particular, the infiltration of macrophages targeting the M2 phenotype opens the door for targeted therapy based on avoiding this phenotype or blocking its function ( 14 , 15 ). According to a large number of clinical trials, the targeted treatment of TAMs can be mainly divided into 3 strategies: preventing TAMs from being recruited to the tumor site, promoting TAM reprogramming to the M1 phenotype, and immune checkpoint blockade ( 16 , 17 ).…”

Section: Introductionmentioning

confidence: 99%

Correlation of tumor-associated macrophage infiltration in glioblastoma with magnetic resonance imaging characteristics: a retrospective cross-sectional study

Zhou,

Xue,

Man

et al. 2023

Quant Imaging Med Surg

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Background Glioblastoma (Gb) is the most common primary malignant tumor of brain with poor prognosis. Immune cells are the main factors affecting the prognosis of Gb, tumor-associated macrophages (TAMs) are the predominant infiltrating immune cell population in the immune microenvironment of Gb. Analyzing the relationship between magnetic resonance imaging (MRI) features and TAMs of Gb, and using imaging features to characterize the infiltration level of TAMs in tumor tissue may provide indicators for clinical decision-making and prognosis evaluation of Gb. Methods Data from 140 in patients with isocitrate dehydrogenase (IDH) wild-type Gb diagnosed via histopathology and molecular diagnosis in the Second Hospital of Lanzhou University from January 2018 to April 2022 were collected in this retrospective, cross-sectional study. MRI images were reviewed for lesion location, cyst, necrosis, hemorrhage, contrast-enhanced T1-weighted MRI signal intensity, average apparent diffusion coefficient (ADCmean), and minimum apparent diffusion coefficient (ADCmin). Immunohistochemical staining with anti-CD163 and anti-CD68 antibodies was employed for macrophage detection. The positive cell percentage was estimated in 9 microscopic fields at 400× magnification per whole-slide image with ImageJ software (National Institutes of Health). Additionally, the relationship between MRI features, molecular, states and the positive CD68 and CD163 expression was analyzed. Results Our study discovered that the mean or median values of CD68+ and CD163+ TAMs were 7.39% and 14.98%, respectively. There was an obvious correlation between CD163+ TAMs and CD68+ TAMs (r=0.497; P=0.000). CD68+ and CD163+ macrophage infiltration correlated with age at diagnosis in patients with Gb (CD68+: r=0.230, P=0.006; CD163+: r=0.172, P=0.042). The levels of Gb TAM infiltration in different tumor locations varied, with the temporal lobe having the highest CD163+ macrophage and CD68+ macrophage infiltration (18.58% and 9.46%, respectively). CD163+ macrophage infiltration was positively correlated with ADCmean (r=0.208; P=0.014). The infiltration of CD68+ macrophages differed significantly between groups with varying degrees of tumor enhancement (H =4.228; P=0.017). There was a significant difference in CD68+ TAMs and CD163+ TAMs between the wild-type and mutant-type telomerase reverse transcriptase (TERT) types (P=0.004 and P=0.031, respectively). Conclusions Age, location of the tumor, degree of tumor enhancement, ADC value, and TERT mutation status were associated with macrophage infiltration. These findings may serve as an effective tool for characterizing the tumor microenvironment in patients with Gb.

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Glioblastoma: two immune subtypes under the surface of the cold tumor

Cited by 5 publications

References 30 publications

Cuproptosis-related gene SLC31A1 expression correlates with the prognosis and tumor immune microenvironment in glioma

Cuproptosis-related gene SLC31A1 expression correlates with the prognosis and tumor immune microenvironment in glioma

Cancer- related protein profile of patient-derived and commercial glioblastoma cell lines exposed to Temozolomide

Correlation of tumor-associated macrophage infiltration in glioblastoma with magnetic resonance imaging characteristics: a retrospective cross-sectional study

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