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Biology
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Immune Microenvironment and Molecular Mechanism of Glioma
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Immune Microenvironment and Molecular Mechanism of Glioma

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

Deadline for manuscript submissions: 31 December 2025 | Viewed by 9262

Special Issue Editor

Dr. Carolina Cristina Jancic

E-Mail Website
Guest Editor
Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX-CONICET), Academia Nacional de Medicina, Buenos Aires 1425, Argentina
Interests: immunology; oncology; infection; gamma/delta T cells; extracellular vesicles

Special Issue Information

Dear Colleagues,

Gliomas are the most common malignant primary brain tumors in adults. Conventionally, gliomas have been classified based on their histology by immunohistochemistry methods. However, in 2016, the World Health Organization (WHO) introduced molecular markers in its classification, enabling a more accurate description and prognosis for these tumors according to their molecular characteristics. Of note, the latest treatment for gliomas is surgical resection, combined with radiotherapy and chemotherapy. However, relapse is common, especially for glioblastomas (GBM; WHO grade IV), which are refractory to standard treatments because of their infiltration nature. Therefore, current therapies are only a temporary and limited solution. More recently, cancer immunotherapy, which has shown impressive results in the treatment of extracranial tumor types, is now being used for GBM treatment. However, disappointing outcomes of clinical studies involving immunotherapy treatment exposed the need for new approaches against GBM. Furthermore, GBM’s microenvironment is rich in immunosuppressive factors, such as cytokines like transforming growth factor-β and IL-10, which can polarize immune cells into a regulatory profile, thus contributing to tumor growth. This Special Issue will focus on original papers covering topics related to “Immune Microenvironment and Molecular Mechanism of Glioma” that present advances in those fields.

Dr. Carolina Cristina Jancic
Guest Editor

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

  • gliomas
  • tumor microenvironment
  • immune response
  • tumor evasion
  • tumor resistance
  • immunotherapy
 

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Published Papers (3 papers)

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Research

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24 pages, 2686 KiB  
Article
Predicting Treatment Outcomes in Glioblastoma: A Risk Score Model for TMZ Resistance and Immune Checkpoint Inhibition
by Nazareno Gonzalez, Melanie Perez Küper, Matias Garcia Fallit, Alejandro J. Nicola Candia, Jorge A. Peña Agudelo, Maicol Suarez Velandia, Ana Clara Romero, Guillermo Agustin Videla-Richardson and Marianela Candolfi
Biology 2025, 14(5), 572; https://doi.org/10.3390/biology14050572 - 20 May 2025
Viewed by 742
Abstract
Glioblastoma (GBM) presents significant therapeutic challenges due to its invasive nature and resistance to standard chemotherapy, i.e., temozolomide (TMZ). This study aimed to identify gene signatures that predict poor TMZ response and high PD−L1/PD−1 tumor expression, and explore potential sensitivity to alternative drugs. [...] Read more.
Glioblastoma (GBM) presents significant therapeutic challenges due to its invasive nature and resistance to standard chemotherapy, i.e., temozolomide (TMZ). This study aimed to identify gene signatures that predict poor TMZ response and high PD−L1/PD−1 tumor expression, and explore potential sensitivity to alternative drugs. We analyzed The Cancer Genome Atlas (TCGA) biopsy data to identify differentially expressed genes (DEGs) linked to these characteristics. Among 33 upregulated DEGs, 5 were significantly correlated with overall survival. A risk score model was built using these 5 DEGs, classifying patients into low-, medium-, and high-risk groups. We assessed immune cell infiltration, immunosuppressive mediators, and epithelial–mesenchymal transition (EMT) markers in each group using correlation analysis, Gene Set Enrichment Analysis (GSEA), and machine learning. The model demonstrated strong predictive power, with high-risk patients exhibiting poorer survival and increased immune infiltration. GSEA revealed upregulation of immune and EMT-related pathways in high-risk patients. Our analyses suggest that high-risk patients may exhibit limited response to PD−1 inhibitors, but could show sensitivity to etoposide and paclitaxel. This risk score model provides a valuable tool for guiding therapeutic decisions and identifying alternative chemotherapy options to enable the development of personalized and cost-effective treatments for GBM patients. Full article
(This article belongs to the Special Issue Immune Microenvironment and Molecular Mechanism of Glioma)
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Review

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35 pages, 2452 KiB  
Review
IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications
by Kristian A. Choate, Evan P. S. Pratt, Matthew J. Jennings, Robert J. Winn and Paul B. Mann
Biology 2024, 13(11), 885; https://doi.org/10.3390/biology13110885 - 30 Oct 2024
Cited by 3 | Viewed by 5054
Abstract
In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced [...] Read more.
In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. IDH enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG). The accumulation of D-2-HG results in epigenetic alterations, oncogenesis and impacts the tumor microenvironment via immunological modulations. Here, we summarize the molecular, cellular, and clinical implications of IDH mutations in gliomas as well as current diagnostic techniques. Full article
(This article belongs to the Special Issue Immune Microenvironment and Molecular Mechanism of Glioma)
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20 pages, 2836 KiB  
Review
Role of T Lymphocytes in Glioma Immune Microenvironment: Two Sides of a Coin
by Laiba Noor, Arun Upadhyay and Vibhuti Joshi
Biology 2024, 13(10), 846; https://doi.org/10.3390/biology13100846 - 21 Oct 2024
Cited by 4 | Viewed by 2752
Abstract
Glioma is known for its immunosuppressive microenvironment, which makes it challenging to target through immunotherapies. Immune cells like macrophages, microglia, myeloid-derived suppressor cells, and T lymphocytes are known to infiltrate the glioma tumor microenvironment and regulate immune response distinctively. Among the variety of [...] Read more.
Glioma is known for its immunosuppressive microenvironment, which makes it challenging to target through immunotherapies. Immune cells like macrophages, microglia, myeloid-derived suppressor cells, and T lymphocytes are known to infiltrate the glioma tumor microenvironment and regulate immune response distinctively. Among the variety of immune cells, T lymphocytes have highly complex and multifaceted roles in the glioma immune landscape. T lymphocytes, which include CD4+ helper and CD8+ cytotoxic T cells, are known for their pivotal roles in anti-tumor responses. However, these cells may behave differently in the highly dynamic glioma microenvironment, for example, via an immune invasion mechanism enforced by tumor cells. Therefore, T lymphocytes play dual roles in glioma immunity, firstly by their anti-tumor responses, and secondly by exploiting gliomas to promote immune invasion. As an immunosuppression strategy, glioma induces T-cell exhaustion and suppression of effector T cells by regulatory T cells (Tregs) or by altering their signaling pathways. Further, the expression of immune checkpoint inhibitors on the glioma cell surface leads to T cell anergy and dysfunction. Overall, this dynamic interplay between T lymphocytes and glioma is crucial for designing more effective immunotherapies. The current review provides detailed knowledge on the roles of T lymphocytes in the glioma immune microenvironment and helps to explore novel therapeutic approaches to reinvigorate T lymphocytes. Full article
(This article belongs to the Special Issue Immune Microenvironment and Molecular Mechanism of Glioma)
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