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Editorial: Immunotherapeutic advances in brain tumours
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DOI：10.3389/fimmu.2026.1949875.png)
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Abstract
En 中文
The interface between immunology and oncology has introduced revolutionary strategies for targeting malignancies; including those within historically complex regions such as the brain. Despite the central nervous system's reputation as an immune-privileged area; recent research validates the potential of immunotherapy in treating both primary and secondary brain tumours. Techniques such as the utilization of dendritic cells primed with tumour-derived materials or RNA and the application of immune checkpoint inhibitors to release brakes on immune responses offer promising pathways to enhance antitumour activity.Antigenic differences between normal and malignant cells of the cancer patient form the rationale for clinical immunotherapeutic strategies. While the central nervous system has traditionally been thought of as an immune-privileged site; studies have been conducted that demonstrate the potential efficacy of immunotherapy in management of primary and secondary brain tumours. Immunization in patients with dendritic cells "fed" derivatives of tumour cells or transfected with tumour-RNA can result in the induction of tumour-specific CD8 + cytotoxic T-lymphocyte (CTL) responses against the patient's malignant cells. In addition; work has been done involving regulation of Immune checkpoint inhibitors which can block molecules involved in inhibiting immune cells that can result in a stimulation of the Tcell response against various tumours including brain tumours. Although results of dendritic cell immunotherapy or checkpoint inhibitors have demonstrated promise in animal models; clinical trials have documented relatively short benefits or limited to a minority of treated patients. In many aggressive tumours; such as gliomas; progression is enabled by local immunosuppression driven by the accumulation of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC). Cytokine gene vaccine therapy involving IL-15 or IL-2 has also been shown in brain tumour animal models to stimulate a potent antitumour immune response and prolong survival.The goal of cancer therapy is the elimination of every remaining tumour cell from the patient. It is unlikely that a single form of therapy can achieve this goal. However; immunotherapy in combination with surgery; radiation therapy and chemotherapy will likely find a place as a new and important means of treatment for patients with brain tumours. Although utilization of immunotherapeutic strategies has proven to be efficacious against a variety of tumours; immunotherapy for treatment of brain tumours has resulted in mixed success with conflicting research findings. Certainly; more work in this field is critically needed. For this special issue papers are being solicited that explore the potential of different immunotherapeutic strategies for the treatment of brain tumours along with related aspects of tumour immunotherapy.This Research Topic aims to explore the forefront of immunotherapy applications for brain tumours; seeking to understand mechanisms; enhance efficacy; and broaden the scope of treatment. Specifically; the research will probe how novel immunotherapeutic strategies can overcome the localized immunosuppression typical of aggressive cancers like gliomas and how they can incite prolonged and potent immune responses against these formidable enemies.Gao et al; in a review entitled; "Emerging frontiers in glioma therapy: the evolving role of glioma vaccines"; emphasized that successful design of glioma vaccines should include biological; immunological and clinical aspects.In this review; they provide an integrative overview of current glioma vaccine strategies; including peptide-based; dendritic cell-based; nucleic acid-based; and autologous tumour-derived platforms; with a particular focus on their biological rationale; clinical performance; and translational limitations. They highlight forward-looking design principles for next-generation glioma vaccines; including improved antigen selection; biomarker-guided patient stratification; microenvironment-aware therapeutic design; and more predictive translational models. Overall; they propose that future progress in glioma vaccine therapy will depend not only on improving vaccine platforms themselves; but also on integrating them into biologically rational and clinically informed therapeutic frameworks.Zhai et al; in a review; "Chimeric antigen receptor macrophages therapy for glioblastoma: challenges and opportunities from preclinical evidence to clinical translation" proposed that macrophages bearing chimeric antigen receptor would be the promising future for glioma therapy.Treatment failure in glioblastoma (GBM) is primarily attributed to the convergence of multiple barriers; including an immunosuppressive tumour microenvironment (TME); intratumoural heterogeneity; and the blood-brain barrier. Chimeric antigen receptor macrophages (CAR-M) therapy presents a promising new avenue for GBM treatment; leveraging its inherent tumour-homing capacity; TME reprogramming function; and potential to bridge innate and adaptive immunity. This review aims to provide a systematic and critical reference to guide the translation of CAR-M therapy from concept to clinical application; a path characterized by both opportunities and challenges.Kiel et al; in a review; "Harnessing immunotherapy: cancer vaccines as novel therapeutic strategies for brain tumour" foresaw that brain cancer therapy would fuse universal vaccines with personalized immunotherapy.Recent advancements in antigen identification and sequencing techniques have catalysed the development of cancer vaccines whose goal is to elicit robust humoral and cellular immune responses against cancer cells. Despite their potential; most cancer vaccines are still in the experimental phase; primarily due to challenges associated with tumour-induced immune suppression. This article explores the role of cancer vaccines in brain cancer; glioblastoma; by providing a granular analysis of clinical trial results and mechanisms of resistance alongside a comparative assessment. This review highlights the potential impact of cancer vaccine clinical trials on future cancer therapies; where effective anti-cancer strategies are within reach. It also provides an in-depth discussion of the brain tumour microenvironment and its influence on vaccine efficacy.Huang et al; in a case report; "Intrathecal administration of PD-1 inhibitor combined with pemetrexed for leptomeningeal metastases from breast cancer: a case report"; presented a promising combination of immunotherapy with chemotherapy.Leptomeningeal metastasis (LM) is a fatal complication of malignant tumours with limited treatment options. This case reports an LM patient from breast cancer treated with intrathecal pemetrexed (15 mg) combined with PD-1 inhibitors (40 mg). The patient showed good tolerance; with no severe adverse events observed; and achieved favourable therapeutic outcomes; including complete resolution of neurological symptoms; negative conversion of cerebrospinal fluid cytology; and significant reduction of imaging-detected lesions. This case provides a new approach to the treatment of LM; suggesting that intrathecal immunotherapy combined with intrathecal chemotherapy may be a safe and effective treatment option; offering valuable insights for future clinical applications.Braitbard et al; in a research report; "Maternal immunization impairs lymphoma growth and CNS/ocular metastasis in the offspring"; demonstrated that the immunity can be transferred through the maternal milk.Maternal immunization is an important tool directed against a variety of infectious maladies in the offspring. Ocular lymphoma is a lethal disease caused mainly by two clinically distinct forms of non-Hodgkin's lymphoma: non-Hodgkin's lymphoma of the central nervous system; or primary CNS lymphoma (PCNSL); and systemic lymphoma metastatic to the eye. Previously; they developed an experimental model whereby mouse lymphoma cell variants; derived from the S49 T-cell lymphoma; metastasized to the CNS and eyes following intraperitoneal inoculation at days 7-10 postnatal. Here; they extended the model to study whether maternal immunization can impede CNS/Ocular metastasis in the offspring exposed to the metastatic lymphoma cells. Immunity was conferred via milk suckling and was prolonged without further challenge for an extended period of at least 3 months. The abovementioned findings constitute a novel experimental model system whereby CNS/Ocular metastasis of malignant lymphoma in the offspring is impeded through maternal vaccination/immunization and thus; can be followed mechanistically as well as for novel therapeutic modalities.Li et al; in a review; "Decoding the immune microenvironment: precision immunotherapy for medulloblastoma subtypes"; correlated the heterogeneity analysis with the improved precision therapy.Medulloblastoma is a severe paediatric brain tumour with distinct molecular subtypes-WNT; SHH; Group 3; and Group 4-each having unique genetic drivers and immune microenvironments. This review highlights the immune characteristics of each subtype: SHH is rich in tumour-associated macrophages (TAMs); whose role in tumourigenesis is debated; Group 3 features cytotoxic T cells often neutralized by immune checkpoints like PD-L1; causing T cell exhaustion; and Group 4 is marked by natural killer (NK) cells and B cells. Understanding the immune microenvironment's subtype-specific heterogeneity in medulloblastoma is crucial for advancing precision immunotherapy and improving patient outcomes.Ali Khan Saddozai; et al; in a research report; "Prognostic value of metal-based ferroptosis and cuproptosis genes and score in lower grade gliomas"; suggested the improved immunotherapy with iron and copper induced cell death.Ferroptosis and Cuproptosis are newly defined forms of cell death. Despite distinct mechanisms; both involve metabolic processes in the TCA cycle and downstream pathways; crucial for anticancer immunity. They evaluated Iron (Fe) and Copper-induced cell death in lower-grade gliomas (LGG) using The Cancer Genome Atlas (TCGA) data by developing a metal-based ferroptosis and cuproptosis genes score (MBFCGs) risk model. The MBFCGs risk model is a promising prognostic tool for LGG; offering insights into underlying mechanisms and new directions for immunotherapy strategies. Assessment of MBFCGs for individual LGG patients may provide clues for developing new immunotherapy strategies.Zhu et al; in a review; "Research progress on the role of dendritic cells in glioma during 1992-2024: a bibliometric analysis"; suggested dendritic cell-based glioma vaccines can be improved by resolving immunosuppression.The extracted literature related to glioma and dendritic cells from 1992 to 2024 using the Web of Science Core Collection. Utilizing Cite Space; Vos viewer and Microsoft Excel; they analyzed the volume of publications; the contributing countries/regions; institutions; authors; journals; references and keywords. The findings suggest that dendritic cells; immunotherapy and glioblastoma treatment will remain the focal points and emerging trends in dendritic cell-glioma research; providing valuable insights for future studies. Dendritic cell vaccines show promise in glioma trials but are hindered by the immunosuppressive tumour microenvironment.Wang et al; in a research report; "scRNA-seq unveils the functional characteristic of gliomaassociated macrophages and the regulatory effect of chlorogenic acid on the immune microenvironment-a study based on mouse models and clinical practice"; chlorogenic acid (CHA) was used in model mice in this study; and scRNA -seq analysis was conducted to elucidate the differentiation trajectories and functional characteristics of bone marrow -derived Mon macrophages (BMDMs) and microglia.A PPI and molecular docking model were constructed using the target prediction database. A case of a patient treated with CHA was reviewed. This study may provide new insights into targeting the regulation of tumour microenvironment (TME) and offer theoretical and practical support for the clinical application of CHA. The results demonstrated the potential of CHA in improving the immune microenvironment and antitumour effects; which could have implications for future glioma treatment strategies. They conclude that the JAK-STAT pathway is the core molecular link between myeloid cells; microglia in the glioma microenvironment; and the action mechanism of CHA.
Keywords:
gene therapy
immunotherapy
brain tumour
brain oncology
brain tumour immunology
Journal
IF:
5.9
Papers:
4.9W
Citations:
22.7W
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Cited Papers