Radiation Spatial Fractionation—A novel approach to integrate Physics, Biology, and Immunology for high therapeutic index radiotherapy

Radiation therapy has the potential to elicit both local and systemic immune responses, which may enhance the effectiveness of immunotherapy (IT). However, the optimal combination of radiation and IT is still under investigation. Spatial Fractionated Radiotherapy (SFRT) represents a cutting-edge technique that delivers focused, high doses to specific tumor subvolumes. This strategic distribution of radiation could stimulate immune cell infiltration in the irradiated tumor, boosting antigen presentation and subsequently activating immune responses in nearby, non-irradiated tumors (the abscopal effect). By adjusting the fractionation and dose distribution across different tumor regions and tissues, SFRT could unlock synergistic biological effects that alter the interplay between the tumor and the immune system.

This Research Topic aims to bridge the fields of physics, biology, and clinical science to uncover the underlying mechanisms by which SFRT influences both local and systemic immune responses. It also seeks to explore potential directions for clinical trials that integrate SFRT into everyday practice and investigate its combination with immune checkpoint inhibitors (ICIs) and cellular therapies.

We welcome contributions covering:
• Basic, translational, and clinical research on SFRT.
• Insights into how various SFRT methods and dose distributions modulate local and systemic immune responses.
• Advances in the physics of delivering SFRT and its biological implications.
• Emerging strategies for combining SFRT with ICIs or cellular therapies to maximize therapeutic outcomes.

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: Spatial Fractionated Radiotherapy, Radiation Therapy, Immune Response, Tumor Microenvironment, Immune Checkpoint Inhibitors

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.