Macrophages in Recurrent Glioblastoma as a Prognostic Factor in the Synergistic System of the Tumor Microenvironment

Montemurro, Nicola; Pahwa, Bhavya; Tayal, Anish; Shukla, Anushruti; Ramirez, Manuel Encarnación; Pena, Issael Jesus Ramirez; Nurmukhametov, Renat; Chavda, Vishal; Carlo, Antonella De

doi:10.3390/neurolint15020037

Cited by 35 publications

(31 citation statements)

References 98 publications

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“…While we did not observe a correlation between IL13Ra2 expression and T-cell infiltration, RNA-Seq data revealed that the group with high IL13Ra2 expression exhibited lower immune and microenvironment scores. Recent research has highlighted the potential role of glioma-associated macrophages in glioblastoma progression and the formation of an immunosuppressive milieu within glioblastomas [ 59 , 60 ]. Likewise, prior studies have identified macrophages as crucial elements in shaping the non-inflammatory tumor environment in DIPG [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Expression of Interleukin-13 Receptor Alpha 2 in Brainstem Gliomas

Li,

Xiao,

Wang

et al. 2024

Cancers

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The objective of this study was to investigate IL13Ra2 expression in brainstem glioma (BSG) and its correlation with key markers, functions, and prognostic implications, evaluating its therapeutic potential. A total of 80 tumor samples from BSG patients were analyzed. Multiplex immunofluorescence was used to examine six markers—IL13Ra2, H3.3K27M, CD133, Ki67, HLA-1, and CD4—establishing relationships between IL13Ra2 and these markers. Survival analysis, employing Kaplan–Meier and Cox proportional hazard regression models, encompassed 66 patients with complete follow-up. RNA-Seq data from a previously published study involving 98 patients were analyzed using the DESeq2 library to determine differential gene expression between groups. Gene Ontology (GO) enrichment and single-sample gene set enrichment analysis (ssGSEA) via the clusterProfiler library were used to delineate the gene functions of differentially expressed genes (DEGs). Nearly all the BSG patients displayed varying IL13Ra2 expression, with 45.0% (36/80) exhibiting over a 20% increase. Elevated IL13Ra2 levels were notably observed in pontine gliomas, diffuse intrinsic pontine gliomas (DIPGs), H3F3A-mutant gliomas, and WHO IV gliomas. IL13Ra2 expression was strongly correlated with H3.3K27M mutant protein, Ki67, and CD133. Patients with IL13Ra2 expression >20% showed shorter overall survival compared to those with ≤20% IL13Ra2 expression. The Cox proportional hazard regression model identified H3F3A mutations, rather than IL13Ra2 expression, as an independent prognostic factor. Analysis of RNA-Seq data from our prior cohort confirmed IL13Ra2’s correlation with H3.3, CD133, and Ki67 levels. Widespread IL13Ra2 expression in BSG, particularly elevated in the H3F3A mutant group, was strongly correlated with H3F3A mutations, increased proliferation, and heightened tumor stemness. IL13Ra2 represents a promising therapeutic target for BSGs, potentially benefiting patients with H3K27M mutations, DIPGs, WHO Grade IV, and pontine location-specific BSGs, particularly those with H3K27M mutations.

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Section: Discussionmentioning

confidence: 99%

Expression of Interleukin-13 Receptor Alpha 2 in Brainstem Gliomas

Li,

Xiao,

Wang

et al. 2024

Cancers

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“…Additionally, our study only analyzed somatic mutations and did not consider other genetic alterations, such as copy number variations and epigenetic modifications, which also play a role in GBM development and progression. Furthermore, the impact of the tumor microenvironment and immune cells, particularly macrophages, on glioma progression and survival has not been considered in our analysis [ 28 , 29 ]. Finally, we did not perform functional assays or in vivo models to validate the mutations of OBSCN or/and AHNAK2 in GBM patients, which makes it difficult to ascertain their clinical implications and their association with favorable survival outcomes.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive somatic mutational analysis in glioblastoma: Implications for precision medicine approaches

Azimi,

Karimpour,

Yazdanian

et al. 2024

PLoS ONE

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Glioblastoma multiforme (GBM), a malignant neoplasm originating from glial cells, remains challenging to treat despite the current standard treatment approach that involves maximal safe surgical resection, radiotherapy, and adjuvant temozolomide chemotherapy. This underscores the critical need to identify new molecular targets for improved therapeutic interventions. The current study aimed to explore the somatic mutations and potential therapeutic targets in GBM using somatic mutational information from four distinct GBM datasets including CGGA, TCGA, CPTAC and MAYO-PDX. The analysis included the evaluation of whole exome sequencing (WES) of GBM datasets, tumor mutation burden assessment, survival analysis, drug sensitivity prediction, and examination of domain-specific amino acid changes. The results identified the top ten commonly altered genes in the aforementioned GBM datasets and patients with mutations in OBSCN and AHNAK2 alone or in combination had a more favorable overall survival (OS). Also, the study identified potential drug sensitivity patterns in GBM patients with mutations in OBSCN and AHNAK2, and evaluated the impact of amino acid changes in specific protein domains on the survival of GBM patients. These findings provide important insights into the genetic alterations and somatic interactions in GBM, which could have implications for the development of new therapeutic strategies for this aggressive malignancy.

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“…In Table 2 and Table 3 , we summarize some research articles where the authors studied cell-free miRNAs as non-invasive biomarkers for the diagnosis and prognosis of brain tumors [ 44 , 45 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ].…”

Section: Cell-free Mirnas As Diagnostic and Prognostic Biomarkersmentioning

confidence: 99%

Cell-Free miRNAs as Non-Invasive Biomarkers in Brain Tumors

Beylerli,

Encarnacion Ramirez,

Shumadalova

et al. 2023

Diagnostics

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Diagnosing brain tumors, especially malignant variants, such as glioblastoma, medulloblastoma, or brain metastasis, presents a considerable obstacle, while current treatment methods often yield unsatisfactory results. The monitoring of individuals with brain neoplasms becomes burdensome due to the intricate tumor nature and associated risks of tissue biopsies, compounded by the restricted accuracy and sensitivity of presently available non-invasive diagnostic techniques. The uncertainties surrounding diagnosis and the tumor’s reaction to treatment can lead to delays in critical determinations that profoundly influence the prognosis of the disease. Consequently, there exists a pressing necessity to formulate and validate dependable, minimally invasive biomarkers that can effectively diagnose and predict brain tumors. Cell-free microRNAs (miRNAs), which remain stable and detectable in human bodily fluids, such as blood and cerebrospinal fluid (CSF), have emerged as potential indicators for a range of ailments, brain tumors included. Numerous investigations have showcased the viability of profiling cell-free miRNA expression in both CSF and blood samples obtained from patients with brain tumors. Distinct miRNAs demonstrate varying expression patterns within CSF and blood. While cell-free microRNAs in the blood exhibit potential in diagnosing, prognosticating, and monitoring treatment across diverse tumor types, they fall short in effectively diagnosing brain tumors. Conversely, the cell-free miRNA profile within CSF demonstrates high potential in delivering precise and specific evaluations of brain tumors.

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Macrophages in Recurrent Glioblastoma as a Prognostic Factor in the Synergistic System of the Tumor Microenvironment

Cited by 35 publications

References 98 publications

Expression of Interleukin-13 Receptor Alpha 2 in Brainstem Gliomas

Expression of Interleukin-13 Receptor Alpha 2 in Brainstem Gliomas

Comprehensive somatic mutational analysis in glioblastoma: Implications for precision medicine approaches

Cell-Free miRNAs as Non-Invasive Biomarkers in Brain Tumors

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