Synergizing Radiation and Immunotherapy in Brain Tumor Management

Neuro-oncology is entering a new era as the convergence of radiotherapy and immunotherapy reshapes the treatment paradigm for brain tumors. Radiation has long been central to managing both primary and metastatic brain malignancies. However, only recently have we begun to appreciate its capacity to modulate the tumor immune microenvironment and, when deliberately integrated with immunotherapeutic strategies, to enhance anti-tumor responses that transcend what either modality achieves alone. With innovations in immunological targeting, radiological delivery, and translational science, there is powerful new momentum to decode and optimize this therapeutic synergy specifically in the context of brain tumors, a setting characterized by unique challenges in immune access, toxicity, and tumor heterogeneity.The objective of this Research Topic is to bring together cutting-edge research that illuminates the true convergence of radiotherapy and immunotherapy in brain tumor management. By fostering work that moves beyond parallel advances to unravel the mechanistic basis for combination strategies, we seek insights into how radiation can be used to actively shape and amplify immune responses within the CNS. We are particularly interested in original findings that clarify optimal scheduling, dosing, and sequencing principles, as well as translational research that bridges laboratory discoveries with early-phase or real-world clinical applications. Through multidisciplinary approaches, novel delivery systems, and innovative trial designs, the goal is to accelerate meaningful clinical progress for both primary and metastatic brain tumors.We are especially interested in work that focuses on, but not limited to, the following themes:• Radiation-driven immune activation and resistance mechanisms in gliomas and brain metastases, particularly studies going beyond checkpoint inhibition alone.• Preclinical or early clinical research specifically evaluating the sequencing, timing, or novel dosing of RT to potentiate distinct arms of immune response.• Innovative delivery platforms (e.g., nanoparticles, exosomes, focused ultrasound) that enable or amplify immune–RT crosstalk within the CNS.• Multimodal biomarker discovery (radiomics, genomics, spatial transcriptomics) predictive of synergistic benefit, translational to clinical trial or real-world contexts.• Prospective or retrospective clinical analyses where patient outcomes or toxicity reflect a mechanistically motivated RT–immunotherapy strategy, not simply combinations by coincidence.Pure immunotherapy or pure radiotherapy studies, unless providing a direct mechanistic or clinical point of convergence, are less aligned with our scope. Join us to accelerate purposeful discovery and clinical translation where radiobiology and immune science spark innovation.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. Topic editors: Johann Matschke, Anja Derer, Udo S Gaipl, Ajay Niranjan, Claire Isabelle Vanpouille-Box Source: https://www.frontiersin.org/research-topics/76387/synergizing-radiation-and-immunotherapy-in-brain-tumor-management