Immunotherapy in Glioblastoma: A Clinical Perspective
Open accessAbstract
Glioblastoma is the most frequent and the most aggressive brain tumor. It is notoriously resistant to current treatments, and the prognosis remains dismal. Immunotherapies have revolutionized the treatment of numerous cancer types and generate great hope for glioblastoma, alas without success until now. In this review, the rationale underlying immune targeting of glioblastoma, as well as the challenges faced when targeting these highly immunosuppressive tumors, are discussed. Innovative immune-targeting strategies including cancer vaccines, oncolytic viruses, checkpoint blockade inhibitors, adoptive cell transfer, and CAR T cells that have been investigated in glioblastoma are reviewed. From a clinical perspective, key clinical trial findings and ongoing trials are discussed for each approach. Finally, limitations, either biological or arising from trial designs are analyzed, and strategies to overcome them are presented. Proof of efficacy for immunotherapy approaches remains to be demonstrated in glioblastoma, but our rapidly expanding understanding of its biology, its immune microenvironment, and the emergence of novel promising combinatorial approaches might allow researchers to finally fulfill the medical need for GBM patients.
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Antigen-based immunotherapies are designed to induce cytotoxic T-cell responses against antigens expressed by the tumour, such as TAAs over-expressed in tumours compared with healthy tissue, resulting in tumour cell death.
“Antigen-based immunotherapies are designed to induce cytotoxic T-cell responses against antigens expressed by the tumour, for example, tumour-associated antigens (TAAs) that are over-expressed in tumours compared with healthy tissue, resulting in tumour cell death [8, 11].”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [8]
Section 5.1 (Vaccine Approaches; page unavailable) says tumour-antigen vaccines aim to induce immune responses and that dendritic-cell vaccines can induce antigen-specific T-cell responses. Section 5.4 (Adoptive Cell Transfer and CAR T Cells; page unavailable) describes T cells attacking cancer cells bearing tumour antigens. The copy does not establish the claim’s specific description of TAAs as over-expressed relative to healthy tissue or explicitly state that these responses result in tumour-cell death. (LLM, conf=0.84)
Experimental — accuracy not yet measuredCheckpoint inhibitors against CTLA-4 and PD-1/PD-L1 have shown only very limited benefits in patients with GBM.
“Immunotherapies such as checkpoint inhibitors against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death-1 (PD-1)/PD ligand 1 (PD-L1) have represented a major advancement in the treatment of several types of solid tumour; however, these treatments have shown only very limited benefits in patients with GBM [7–9].”
From Preclinical development of an mRNA-based multiepitope immunotherapeutic for glioblastoma (2025) · cites this paper as [8]
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“…options for GBM. Antigen-based immunotherapies are designed to induce cytotoxic T-cell responses against antigens expressed by the tumour, for example, tumour-associated antigens (TAAs) that are over-expressed in tumours compared with healthy tissue, resulting in tumour cell death [8, 11].”
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- Authors
- Desbaillets, N., & Hottinger, A. F.
- Affiliations
- Centre Hospitalier Universitaire Vaudois (CH)
- Corresponding author
- Hottinger, Andreas Felix
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2021-07-24
- Volume
- 13
- Issue
- 15
- Pages
- 3721
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC8345081
- OpenAlex
- W3185517073
- Cited by
- 31
- References
- 134
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 6 · 2021: 4
- FWCI
- 0.85
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SERVAL (Université de Lausanne) (publishedVersion, cc-by)
- IRIS (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Centre Hospitalier Universitaire Vaudois
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- glioblastoma, cancer immunotherapy, tumor immune microenvironment, immunosuppression, cancer vaccines, oncolytic viruses, immune checkpoint inhibitors, adoptive cell transfer, chimeric antigen receptor T cells, clinical trials, combination therapy
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