Interferon-Based Therapeutic Strategies for Gliomas

Gliomas, particularly high-grade subtypes such as glioblastoma, present formidable challenges owing to invasive growth, genetic heterogeneity and an immunosuppressive microenvironment. Interferons (IFNs) have emerged as multitargeted cytokines capable of modulating both tumour-intrinsic pathways and host immunity. Type I interferons (IFN-α, IFN-β) exert direct antiproliferative effects by inducing cell-cycle arrest and apoptosis via STAT1-dependent transcriptional programmes, while simultaneously enhancing antigen presentation and stimulating the recruitment of tumour-infiltrating lymphocytes. Type II interferon (IFN-γ) further augments antitumour responses by upregulating major histocompatibility complex expression and promoting cytotoxic T-cell activation. Therapeutic approaches include systemic administration, local gene therapy using viral vectors and engineered co-formulations designed to synergistically disrupt mitotic checkpoints. Combining IFNs with standard treatments such as temozolomide, radiotherapy or immune checkpoint inhibitors has shown promise in overcoming resistance mechanisms, including DNA-repair enzyme induction and persistence of glioma stem-like cells. Preclinical studies indicate that IFN-based regimens can selectively target glioma stem cells, reprogram mesenchymal signatures and normalise tumour vasculature. As clinical translation progresses, optimisation of dosing regimens, vector delivery and combination sequencing remains essential to maximise the therapeutic index of interferon strategies in glioma management.

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Interferon-Based Therapeutic Strategies for Gliomas publication trend

The graph below shows the total number of articles in interferon-based therapeutic strategies for gliomas across all publications each year (not limited to Nature Index journals).

Technical terms

Type I interferon: A class of cytokines including interferon-α and interferon-β, with antiviral, antiproliferative and immunomodulatory functions.

Type II interferon: Interferon-γ, a cytokine that augments antigen presentation and activates macrophages and cytotoxic T cells.

Glioma stem cell (GSC): A subpopulation of tumour cells with self-renewal and differentiation capacity, contributing to tumour initiation and recurrence.

Tumour microenvironment (TME): The cellular and molecular milieu surrounding a tumour, including immune cells, vasculature and extracellular matrix.

Cell-cycle arrest: The halting of cell-division progression at a specific checkpoint, often induced to prevent proliferation of damaged cells.

Mesenchymal phenotype: A cellular state characterised by enhanced motility and invasiveness, often associated with therapy resistance in gliomas.

Adeno-associated viral (AAV) vector: A non-pathogenic viral delivery system used for gene therapy to achieve sustained expression of therapeutic transgenes in target tissues.

References

1. Harnessing type I interferon-mediated immunity to target malignant brain tumors. Frontiers in Immunology (2023).
2. JCOG0911 INTEGRA study: a randomized screening phase II trial of interferonβ plus temozolomide in comparison with temozolomide alone for newly diagnosed glioblastoma. Journal of Neuro-Oncology (2018).
3. Intracranial AAV‐IFN‐β gene therapy eliminates invasive xenograft glioblastoma and improves survival in orthotopic syngeneic murine model. Molecular Oncology (2017).
4. A co-formulation of interferons alpha2b and gamma distinctively targets cell cycle in the glioblastoma-derived cell line U-87MG. BMC Cancer (2023).
5. Intrinsic Interferon Signaling Regulates the Cell Death and Mesenchymal Phenotype of Glioblastoma Stem Cells. Cancers (2021).
6. Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy. Frontiers in Immunology (2021).