Immunotherapy and Vaccination Strategies in Glioblastoma: Optimizing Survival Through Better Trial Design and Stratification

Glioblastoma remains one of the most lethal primary brain tumors, with limited durable benefit from current standard-of-care approaches. In parallel, immunotherapy and therapeutic vaccination strategies have generated strong biological rationale and encouraging signals in selected settings, yet many clinical trials have not translated into consistent survival gains across broader patient populations. This gap highlights a core challenge in glioblastoma immuno-oncology: not only identifying effective immune-based interventions but also designing trials that can detect true benefit in a disease marked by profound intratumoral heterogeneity, an immunosuppressive microenvironment, treatment-induced immune modulation, and variable clinical trajectories.

This Research Topic will bring together basic, translational, and clinical contributions that examine immunotherapy and vaccination strategies in glioblastoma through the lens of trial optimization and patient stratification. We welcome work that clarifies which biological and clinical features define immunotherapy-responsive subgroups, how biomarkers should be integrated into eligibility and endpoints, and which trial designs best account for time-varying therapies, crossover, pseudoprogression, steroid exposure, and evolving standards of care. The Topic aims to be broadly relevant to investigators developing immune-based treatments, clinical trialists, computational scientists working on stratification, and clinicians interpreting response in routine practice.

Areas of interest include, but are not limited to:

o Therapeutic vaccination approaches (e.g., peptide/protein, dendritic cell, neoantigen, viral or nucleic-acid-based platforms), combination strategies, and mechanisms of resistance

o Checkpoint inhibition, cellular therapies, and innate immune modulation in glioblastoma, including rationale for combination with vaccines, radiation, targeted agents, or standard chemoradiation

o Biomarker development and validation for treatment selection and monitoring, including tumor- and blood-based markers, immune profiling, radiomic features, and longitudinal sampling strategies

o Patient stratification frameworks incorporating molecular subtype, MGMT status, tumor location/volume, immune contexture, steroid use, performance status, prior therapies, and extent of resection

o Trial design innovations such as adaptive/enrichment designs, platform trials, Bayesian approaches, window-of-opportunity studies, and pragmatic strategies for multi-center feasibility

o Endpoints and response assessment specific to immunotherapy in neuro-oncology, including RANO/iRANO considerations, pseudoprogression, immunotherapy-related adverse events, and patient-reported outcomes

o Methodological and statistical approaches to reduce bias and improve interpretability (e.g., handling crossover, delayed effects, competing risks, and heterogeneity of post-progression care)

o Translational models and correlative science that connect immune mechanisms to clinical outcomes and inform rational stratification

By focusing on how we test immunotherapies and vaccines—alongside what we test—this Research Topic seeks to accelerate more informative, biomarker-driven trials and improve the likelihood of meaningful survival benefit for patients with glioblastoma.




Please note: Manuscripts consisting solely of bioinformatics, computational analysis, or predictions of public databases which are not accompanied by validation (independent clinical or patient cohort, or biological validation in vitro or in vivo, which are not based on public databases) are not suitable for publication in this journal.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• ... View all formats

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Glioblastoma, Immunotherapy, Therapeutic cancer vaccines, Biomarkers, Patient stratification, Clinical trial design, Immune tumor microenvironment

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.