Dendritic-Cell Vaccines and Cytokine-Induced Killer Cell Immunotherapy for Glioblastoma: A Translational Review of Biological Rationale, Clinical Evidence, and Combination Strategies

Glioblastoma, IDH-wildtype, CNS WHO grade 4, is an infiltrative and immunologically complex adult-type diffuse glioma with poor prognosis despite maximal safe resection, radiotherapy, temozolomide, and selected use of tumor-treating fields. The current histomolecular definition of glioblastoma, together with its antigenic heterogeneity, myeloid-rich tumor microenvironment, blood-brain/tumor barrier, treatment-induced lymphopenia, and corticosteroid-associated immunosuppression, creates major challenges for immunotherapy. Dendritic-cell vaccines and cytokine-induced killer cell-based therapy provide complementary biological solutions. Dendritic-cell vaccines can process broad tumor-antigen repertoires and prime adaptive antitumor immunity, whereas CIK cells provide ex vivo-expanded cytotoxic effector function with T-cell and natural killer-like properties. This review synthesizes developments over the last decade in glioblastoma-directed DC vaccination, CIK-cell therapy, and DC-CIK strategies, while situating them within the broader landscape of surgery, radiochemotherapy, tumor-treating fields, immune checkpoint blockade, CAR-T cells, oncolytic virotherapy, anti-angiogenic therapy, and recurrent-disease management. Current evidence supports the safety and biological plausibility of DC and CIK-based immunotherapy, with encouraging survival signals from DCVax-L and randomized CIK-cell studies. However, definitive implementation requires molecularly homogeneous cohorts, standardized GMP-compliant manufacturing, validated potency assays, steroid-adjusted immune monitoring, biomarker-guided patient selection, and rational combination designs. DC and DC-CIK platforms should therefore be viewed not as isolated alternatives but as immune-amplifying components of multimodal neuro-oncology.