Glioblastoma Microenvironment: From an Inviolable Defense to a Therapeutic Chance

Nunno, Vincenzo Di; Franceschi, Enrico; Tosoni, Alicia; Gatto, Lidia; Bartolini, Stefania; Brandes, Alba Ariela

doi:10.3389/fonc.2022.852950

Cited by 15 publications

(11 citation statements)

References 157 publications

(260 reference statements)

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“…Besides, it is well-known that TME has an important role during the progression of human cancers, as well as the OS after the operation. , Presently, the heterogeneity of the molecular subtypes of BC patients was also explored by the single-cell analysis on GSE118389. The results demonstrate that most of the key prognosis-related gene classification signatures are distributed in immune cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of Breast Cancer Subtypes by Integrating Genomic Analysis with the Immune Microenvironment

Ding

Liu

et al. 2023

ACS Omega

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Objectives: We aim to identify the breast cancer (BC) subtype clusters and the crucial gene classifier prognostic signatures by integrating genomic analysis with the tumor immune microenvironment (TME). Methods: Data sets of BC were derived from the Cancer Genome Atlas (TCGA), METABRIC, and Gene Expression Omnibus (GEO) databases. Unsupervised consensus clustering was carried out to obtain the subtype clusters of BC patients. Weighted gene coexpression network analysis (WGCNA), least absolute shrinkage and selection operator (LASSO), and univariate and multivariate regression analysis were employed to obtain the gene classifier signatures and their biological functions, which were validated by the BC dataset from the METABRIC database. Additionally, to evaluate the overall survival rates of BC patients, Kaplan−Meier survival analysis was carried out. Moreover, to assess how BC subtype clusters are related to the TME, single-cell analysis was performed. Finally, the drug sensitivity and the immune cell infiltration for different phenotypes of BC patients were also calculated by the CIBERSORT and ESTIMATE algorithms. Results: TCGA−BC samples were divided into three subtype clusters, S1, S2, and S3, among which the prognosis of S2 was poor and that of S1 and S3 were better. Three key pathways and 10 crucial prognostic-related gene signatures are screened. Finally, single-cell analysis suggests that S1 samples have the most types of immune cells, S2 with more sensitivity to tumor treatment drugs are enriched with more neutrophils, and more multilymphoid progenitor cells are involved in subtype cluster S3. Conclusions: Our novelty was to identify the BC subtype clusters and the gene classifier signatures employing a large-amount dataset combined with multiple bioinformatics methods. All of the results provide a basis for clinical precision treatment of BC.

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Section: Discussionmentioning

confidence: 99%

Identification of Breast Cancer Subtypes by Integrating Genomic Analysis with the Immune Microenvironment

Ding

Liu

et al. 2023

ACS Omega

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“…Microenvironment enriched in microglia and macrophage concentration (33)(34)(35) with low lymphocytes Recruitment of monocytes by secretion of CCL2-7, GDNF, TNF, CSF-1, and GM-CSF (7,36). Lower percentage of CD8+PD1 +, CD4+ TIM3+, and regulatory T cells is associated with a less immune-suppressive stroma (37).…”

Section: Microenvironment Of Idh-mutated Gliomasmentioning

confidence: 99%

“…Macrophages are associated with immunesuppressive stroma mainly due to the secretion of TGFb (7,36).…”

Section: Microenvironment Of Idh-mutated Gliomasmentioning

confidence: 99%

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Tumor-Associated Microenvironment of Adult Gliomas: A Review

et al. 2022

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The glioma-associated tumor microenvironment involves a multitude of different cells ranging from immune cells to endothelial, glial, and neuronal cells surrounding the primary tumor. The interactions between these cells and glioblastoma (GBM) have been deeply investigated while very little data are available on patients with lower-grade gliomas. In these tumors, it has been demonstrated that the composition of the microenvironment differs according to the isocitrate dehydrogenase status (mutated/wild type), the presence/absence of codeletion, and the expression of specific alterations including H3K27 and/or other gene mutations. In addition, mechanisms by which the tumor microenvironment sustains the growth and proliferation of glioma cells are still partially unknown. Nonetheless, a better knowledge of the tumor-associated microenvironment can be a key issue in the optic of novel therapeutic drug development.

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“…Glioma stem cells (GSCs) are a small subpopulation of cells within the GB, with genomic instability, self-renewal and tumor-initiating capacity, and the ability to differentiate into different GB subpopulations, being responsible for tumor heterogeneity [ 24 , 25 , 26 , 27 ]. Moreover, GSCs are resistant to apoptosis [ 28 , 29 , 30 , 31 ], can modulate the components of the tumor microenvironment (TME), are involved in angiogenesis activation and immunosuppression and drive radio/chemoresistance [ 22 , 32 , 33 ]. The inability of current therapies to eliminate specific GSC subpopulations has been considered a major factor contributing to the inevitable recurrence after treatment [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Glioblastoma Therapy: Past, Present and Future

Obrador,

Moreno-Murciano,

Oriol-Caballo

et al. 2024

IJMS

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Glioblastoma (GB) stands out as the most prevalent and lethal form of brain cancer. Although great efforts have been made by clinicians and researchers, no significant improvement in survival has been achieved since the Stupp protocol became the standard of care (SOC) in 2005. Despite multimodality treatments, recurrence is almost universal with survival rates under 2 years after diagnosis. Here, we discuss the recent progress in our understanding of GB pathophysiology, in particular, the importance of glioma stem cells (GSCs), the tumor microenvironment conditions, and epigenetic mechanisms involved in GB growth, aggressiveness and recurrence. The discussion on therapeutic strategies first covers the SOC treatment and targeted therapies that have been shown to interfere with different signaling pathways (pRB/CDK4/RB1/P16ink4, TP53/MDM2/P14arf, PI3k/Akt-PTEN, RAS/RAF/MEK, PARP) involved in GB tumorigenesis, pathophysiology, and treatment resistance acquisition. Below, we analyze several immunotherapeutic approaches (i.e., checkpoint inhibitors, vaccines, CAR-modified NK or T cells, oncolytic virotherapy) that have been used in an attempt to enhance the immune response against GB, and thereby avoid recidivism or increase survival of GB patients. Finally, we present treatment attempts made using nanotherapies (nanometric structures having active anti-GB agents such as antibodies, chemotherapeutic/anti-angiogenic drugs or sensitizers, radionuclides, and molecules that target GB cellular receptors or open the blood–brain barrier) and non-ionizing energies (laser interstitial thermal therapy, high/low intensity focused ultrasounds, photodynamic/sonodynamic therapies and electroporation). The aim of this review is to discuss the advances and limitations of the current therapies and to present novel approaches that are under development or following clinical trials.

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Glioblastoma Microenvironment: From an Inviolable Defense to a Therapeutic Chance

Cited by 15 publications

References 157 publications

Identification of Breast Cancer Subtypes by Integrating Genomic Analysis with the Immune Microenvironment

Identification of Breast Cancer Subtypes by Integrating Genomic Analysis with the Immune Microenvironment

Tumor-Associated Microenvironment of Adult Gliomas: A Review

Glioblastoma Therapy: Past, Present and Future

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