Stereotactic radiotherapy as an immune catalyst: Biomarkers, mechanisms, and therapeutic synergies

Radiotherapy (RT) has evolved from a purely local treatment into a key modulator of antitumor immunity. Precision techniques such as stereotactic body radiotherapy (SBRT), stereotactic radiosurgery (SRS), and advanced delivery modalities are capable of inducing immunogenic cell death, enhancing antigen release and presentation, activating innate immune pathways, and reshaping the tumor microenvironment (TME). The balance between immunostimulatory and immunosuppressive effects depends on dose, fractionation schedules, sequencing with immunotherapy, and intrinsic TME characteristics. At the same time, novel imaging approaches, radiomics, spatial profiling, and single-cell technologies are offering unprecedented insights into immune dynamics before, during, and after radiation treatment. As the field moves rapidly toward tailored multimodal strategies, better understanding of radiation-driven immune mechanisms is critical for improving outcomes in solid tumors.The goal of this Research Topic is to deepen our understanding of how radiotherapy can be strategically leveraged as an immune-modulating intervention, capable of overcoming resistance to immunotherapy. Despite the transformative impact of immune checkpoint inhibitors, many solid tumors remain immunologically “cold” or fail to mount durable responses. High-precision radiotherapy offers a unique opportunity to convert these non-inflamed tumors into more immunogenic phenotypes by triggering antigen release, activating cytosolic DNA-sensing pathways such as cGAS-STING, enhancing T-cell recruitment, and altering the suppressive composition of the TME.Through multidisciplinary contributions that integrate radiobiology, immunology, physics, imaging sciences, bioinformatics, and clinical oncology, this Research Topic aims to identify actionable biomarkers and mechanistic insights that can guide patient selection, dose/fractionation strategies, and treatment sequencing. The ultimate objective is to advance the development of personalized, mechanism-driven immuno-radiotherapy approaches that improve response rates, durability of benefit, and overall clinical outcomes for patients with solid tumors.This Research Topic invites contributions focused on the immunological effects of radiotherapy and its integration with immunotherapy across basic, translational, and clinical domains. We welcome original research, reviews, mini-reviews, and methodological papers addressing topics such as:• Immunomodulatory mechanisms induced by SBRT, SRS, and high-dose-rate or hypofractionated radiotherapy.• Dose and fractionation schemes optimized for immune activation and the concept of “immunogenic dose shaping.”• Biomarkers predicting response or resistance to combined RT + immune checkpoint inhibition.• Radiomics, artificial intelligence, and advanced imaging to non-invasively track immune changes after radiation.• Interaction between radiation, T-cell exhaustion, myeloid-driven immunosuppression, stromal remodeling, and vascular reprogramming.• Optimal sequencing of radiotherapy and immunotherapy (concurrent versus sequential strategies).• Early-phase clinical trials and real-world evidence evaluating innovative immuno-radiotherapy regimens. Topic editors: Antonio Pontoriero, Gianluca Ferini Source: https://www.frontiersin.org/research-topics/77718/stereotactic-radiotherapy-as-an-immune-catalyst-biomarkers-mechanisms-and-therapeutic-synergies