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Biology
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Biomarkers and Immunotherapeutic Targets in Glioblastoma
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Biomarkers and Immunotherapeutic Targets in Glioblastoma

A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Cancer Biology".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 9525

Special Issue Editors

Dr. Jiao Wang

E-Mail Website
Guest Editor
Purdue College of Pharmacy, Heine Pharmacy Building 575 Stadium Mall Drive West Lafayette, IN 47907-2091, USA
Interests: cancer cells; tumor microenvironment; cancer biology; cell culture; tumor biology; tumor cell culture
Dr. Sandro Matosevic

E-Mail Website
Guest Editor
Purdue College of Pharmacy, Heine Pharmacy Building 575 Stadium Mall Drive, West Lafayette, IN 47907-2091, USA
Interests: cancer immunotherapy; cell-based therapies; immunoengineering; natural killer cells; immuno-oncology; synthetic biology; biopharmaceutical engineering

Special Issue Information

Glioblastoma, also called GBM, the most aggressive type of primary brain tumor, makes up about 15% of all brain tumors and is projected to be diagnosed in nearly 210,000 people globally each year. Despite aggressive treatment with surgery, radiation, and chemotherapy, GBM remains an incurable tumor with a median survival of only 15 months. Immunotherapy has seen great success in the treatment of various types of cancer, from melanoma to lung, breast, colorectal, kidney, and even some brain cancers. Accordingly, this type of therapy may give us a lot of hope and act as the future of GBM treatment. To date, GBM has not been among immunotherapy success stories yet due to several obstacles including the highly immunosuppressive nature of GBM and the limitations of the immune response in the central nervous system. Currently, a diverse set of biomarkers such as different checkpoint molecules have already been well investigated and implicated as potential immunotherapeutic targets and prognostic indicators in some types of cancers. Therefore, understanding the biomarkers for appropriate patient selection as well as tumor progression are necessary for implementation of immunotherapy for GBM. Additionally, the combination of immune therapies driven by these biomarkers would be the key for the future of immunotherapy for GBM. This Special Issue welcomes the submission of original research and review manuscripts focusing on biomarkers of interest for the diagnosis, therapy, an theranostics of GBM, but also on the specific technologies employed in their identification and targeting, helping us to achieve a realistic overview of this exciting and interdisciplinary field of biomedical research. It is envisioned that this Special Issue will help readers to become more familiar with advances in the discovery and development of effective immunotherapeutic treatments for the devastating GBM.

Dr. Jiao Wang
Dr. Sandro Matosevic
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biology is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Glioblastoma, also called GBM, the most aggressive type of primary brain tumor. Despite aggressive treatment with surgery, radiation, and chemotherapy, GBM remains an incurable tumor with a median survival of only 15 months. Immunotherapy has seen great success in the treatment of various types of cancer, this type of therapy may give us a lot of hope and act as the future of GBM treatment. To date, GBM has not been among immunotherapy success stories yet due to several obstacles. Currently, a diverse set of biomarkers such as different checkpoint molecules have already been well investigated and implicated as potential immunotherapeutic targets and prognostic indicators in some types of cancers. Therefore,  the combination of immune therapies driven by these biomarkers would be the key for the future of immunotherapy for GBM.
This Special Issue welcomes the submission of original research and review manuscripts focusing on biomarkers of interest for the diagnosis, therapy, an theranostics of GBM, but also on the specific technologies employed in their identification and targeting.

Published Papers (3 papers)

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Research

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22 pages, 3991 KiB  
Article
Identification of Prominent Genes between 3D Glioblastoma Models and Clinical Samples via GEO/TCGA/CGGA Data Analysis
by Brandon Wee Siang Phon, Saatheeyavaane Bhuvanendran, Qasim Ayub, Ammu Kutty Radhakrishnan and Muhamad Noor Alfarizal Kamarudin
Biology 2023, 12(5), 648; https://doi.org/10.3390/biology12050648 - 25 Apr 2023
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Abstract
A paradigm shift in preclinical evaluations of new anticancer GBM drugs should occur in favour of 3D cultures. This study leveraged the vast genomic data banks to investigate the suitability of 3D cultures as cell-based models for GBM. We hypothesised that correlating genes [...] Read more.
A paradigm shift in preclinical evaluations of new anticancer GBM drugs should occur in favour of 3D cultures. This study leveraged the vast genomic data banks to investigate the suitability of 3D cultures as cell-based models for GBM. We hypothesised that correlating genes that are highly upregulated in 3D GBM models will have an impact in GBM patients, which will support 3D cultures as more reliable preclinical models for GBM. Using clinical samples of brain tissue from healthy individuals and GBM patients from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), Chinese Glioma Genome Atlas (CGGA), and Genotype-Tissue Expression (GTEx) databases, several genes related to pathways such as epithelial-to-mesenchymal transition (EMT)-related genes (CD44, TWIST1, SNAI1, CDH2, FN1, VIM), angiogenesis/migration-related genes (MMP1, MMP2, MMP9, VEGFA), hypoxia-related genes (HIF1A, PLAT), stemness-related genes (SOX2, PROM1, NES, FOS), and genes involved in the Wnt signalling pathway (DKK1, FZD7) were found to be upregulated in brain samples from GBM patients, and the expression of these genes were also enhanced in 3D GBM cells. Additionally, EMT-related genes were upregulated in GBM archetypes (wild-type IDH1R132 ) that historically have poorer treatment responses, with said genes being significant predictors of poorer survival in the TCGA cohort. These findings reinforced the hypothesis that 3D GBM cultures can be used as reliable models to study increased epithelial-to-mesenchymal transitions in clinical GBM samples. Full article
(This article belongs to the Special Issue Biomarkers and Immunotherapeutic Targets in Glioblastoma)
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21 pages, 5714 KiB  
Article
The Tropomyosin Family as Novel Biomarkers in Relation to Poor Prognosis in Glioma
by Ke Huang, Huihui Wang, Jia Xu, Ruiming Xu, Zelin Liu, Yi Li and Zhaoqing Xu
Biology 2022, 11(8), 1115; https://doi.org/10.3390/biology11081115 - 26 Jul 2022
Cited by 4 | Viewed by 2001
Abstract
(1) Background: The functions of the tropomyosin (TPM) family in tumors and cancers have been explored; however, striking differences have been observed. This study aims to further our understanding of the effects of TPMs in glioma, and find novel biomarkers for glioma. (2) [...] Read more.
(1) Background: The functions of the tropomyosin (TPM) family in tumors and cancers have been explored; however, striking differences have been observed. This study aims to further our understanding of the effects of TPMs in glioma, and find novel biomarkers for glioma. (2) Methods: RNA-seq data were downloaded from TCGA and GTEx. Survival analyses, Cox regression, nomogram, calibration curves, ROC curves, gene function enrichment analyses, and immune cell infiltration analyses were carried out using R. CCK8 assay, while Brdu assay, colony formation assay, and Transwell assay were used to verify the functions of TPM3 in glioma. (3) Results: TPM1/3/4 were significantly more highly expressed in glioma than that in normal tissues, while higher expression of TPM2/3/4 was correlated with a worse overall survival than lower expression of TPM2/3/4. Furthermore, bioinformatic analyses indicated that TPM3/4 could be promoting factors for poorer survival in glioma, but only TPM3 could serve as an independent prognostic factor. Gene function analyses showed that TPMs may be involved in immune responses. Moreover, further experimental investigations verified that TPM3 overexpression enhanced the proliferation and tumorigenicity of glioma. (4) Conclusions: High expression of TPM3/4 was positively correlated with poorer prognosis in glioma, and TPM3 could serve as a novel independent prognostic factor of glioma. Full article
(This article belongs to the Special Issue Biomarkers and Immunotherapeutic Targets in Glioblastoma)
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Review

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15 pages, 12086 KiB  
Review
Preoperative Stereotactic Radiosurgery for Glioblastoma
by Eric J. Lehrer, Henry Ruiz-Garcia, Anthony D. Nehlsen, Kunal K. Sindhu, Rachel Sarabia Estrada, Gerben R. Borst, Jason P. Sheehan, Alfredo Quinones-Hinojosa and Daniel M. Trifiletti
Biology 2022, 11(2), 194; https://doi.org/10.3390/biology11020194 - 26 Jan 2022
Cited by 10 | Viewed by 4514
Abstract
Glioblastoma is a devastating primary brain tumor with a median overall survival of approximately 15 months despite the use of optimal modern therapy. While GBM has been studied for decades, modern therapies have allowed for a reduction in treatment-related toxicities, while the prognosis [...] Read more.
Glioblastoma is a devastating primary brain tumor with a median overall survival of approximately 15 months despite the use of optimal modern therapy. While GBM has been studied for decades, modern therapies have allowed for a reduction in treatment-related toxicities, while the prognosis has largely been unchanged. Adjuvant stereotactic radiosurgery (SRS) was previously studied in GBM; however, the results were disappointing. SRS is a highly conformal radiation technique that permits the delivery of high doses of ionizing radiation in 1–5 sessions while largely sparing surrounding healthy tissues. Furthermore, studies have shown that the delivery of ablative doses of ionizing radiation within the central nervous system is associated with enhanced anti-tumor immunity. While SRS is commonly used in the definitive and adjuvant settings for other CNS malignancies, its role in the preoperative setting has become a topic of great interest due to the potential for reduced treatment volumes due to the treatment of an intact tumor, and a lower risk of nodular leptomeningeal disease and radiation necrosis. While early reports of SRS in the adjuvant setting for glioblastoma were disappointing, its role in the preoperative setting and its impact on the anti-tumor adaptive immune response is largely unknown. In this review, we provide an overview of GBM, discuss the potential role of preoperative SRS, and discuss the possible immunogenic effects of this therapy. Full article
(This article belongs to the Special Issue Biomarkers and Immunotherapeutic Targets in Glioblastoma)
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