REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1639521
This article is part of the Research TopicPredictive Biomarkers to Immune Checkpoint Inhibitors in Lung CancerView all 4 articles
Immune checkpoints in immune response to glioma: two sides of the same coin
Provisionally accepted
- 1Institute of Bioorganic Chemistry (RAS), Moscow, Russia
- 2Moskovskij fiziko-tehniceskij institut nacional'nyj issledovatel'skij universitet, Dolgoprudny, Russia
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Gliomas are aggressive brain tumors of glial origin accounting for about 80% of the central nervous system (CNS) malignancies. Glioma cells are known to form a highly immunosuppressive tumor microenvironment (TME) capable of inhibiting T cell activation and protecting tumors from elimination by the immune system. One of the predominant immune inhibitory mechanisms in the TME are immune checkpoints: a complex system of membrane-bound ligands on tumor and immune cells that interact with surface receptors on T lymphocytes and affect their activation and cytotoxicity. There is mounting evidence regarding the role of immune checkpoints expressed in gliomas, in particular, their most aggressive formglioblastoma multiforme (GBM). In this review, we discuss the immune checkpoints with proven expression in gliomas, their ligands, related signaling pathways, co-expression profiles, and the effects of immune cells on antitumor activity. We collected data not only on the canonical immune checkpoints (e.g. PD-1/PD-L1 or CTLA-4) but also on novel and alternative ones including soluble mediators and enzymes. We review data describing the correlation of immune checkpoint expression with patient survival as well as co-expression with other molecules involved in glioma development. Where possible, we analyzed the differences between immune checkpoints in low-grade (LGG) and high-grade gliomas (HGG). Negative effects of several immune checkpoints on T cells could be eliminated by therapeutic monoclonal antibodies that block the interaction between checkpoint ligands and receptors. Therefore, alongside with traditional approaches and T cell-based immunotherapy, the antibody-mediated blockade of immune checkpoints could be considered as a potentially promising therapeutic approach against gliomas.
Keywords: Glioma, Glioblastoma, immune response, immune checkpoints, t cell exhaustion, myeloid suppressor cells, regulatory T cells, immune checkpoint inhibitors
Received: 02 Jun 2025; Accepted: 29 Jul 2025.
Copyright: © 2025 Musatova, Kumar, Vinogradov and Rubtsov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yury Rubtsov, Institute of Bioorganic Chemistry (RAS), Moscow, Russia
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