Combining Radiation Therapy with Immunotherapies: Mechanisms, Challenges, and Clinical Advances

Radiation therapy (RT) is an essential component of cancer treatment, and the emergence of immunotherapies, including immune checkpoint inhibitors, CAR T-cell therapies, bispecific antibodies, and novel immune modulators, has reshaped the prospects for many patients. Therapies that integrate RT with innovative immunotherapies are opening new avenues for durable responses and improved outcomes across both solid tumors and hematologic malignancies.

Despite progress, significant clinical and translational questions remain regarding how best to develop, personalize, and implement these combinations in routine practice. Clarifying the underlying biological mechanisms, optimizing sequencing and dosing strategies, and developing reliable biomarkers for response prediction and toxicity management are all critical to advancing these new therapeutic approaches.

This Research Topic welcomes original research, reviews, and clinical studies that address, but are not limited to:
• How radiation interacts with the immune system when combined with emerging immunotherapeutic agents.
• Discovery and validation of biomarkers that inform patient selection or predict clinical outcomes in RT–immunotherapy regimens.
• Innovative laboratory and preclinical models that inspire new combination strategies.
• Results from clinical trials, prospective studies, and real-world data involving combinatorial regimens.
• Approaches to managing unique toxicities, resistance, and challenges in integrating combined therapies into patient care.
• The development and application of advanced technologies, including imaging and computational tools, supporting the monitoring and guidance of integrated therapies.

By spanning molecular research, translational advances, clinical trials, and implementation science, this collection aims to drive progress in developing safe and effective integration of RT and immunotherapies, ultimately moving toward more personalized and durable cancer treatment.

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.

Keywords: Radiation Therapy, Immunotherapy, Combination Therapy, CAR T-cell, Bispecific Antibodies, Therapeutic Modulators, Clinical Trials, Translational Science, Biomarkers, Toxicity, Patient Outcomes

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.