Novel Radiotherapy and Tumor Immunity: From Mechanisms of Radiosensitization to Overcoming Radioresistance

The field of oncology has seen remarkable advances with the emergence of innovative radiotherapy modalities, including FLASH radiotherapy, Boron Neutron Capture Therapy (BNCT), Lattice Radiotherapy, Spatially Fractionated Radiation Therapy (SFRT), precision particle therapy, immunomodulatory stereotactic body radiotherapy (SBRT), and next-generation particle therapy (e.g., immune-optimized carbon ion therapy, etc.). Despite their promise in directly eradicating tumor cells, the persistent challenges of tumor radioresistance and suboptimal immune engagement hinder enduring tumor control and overall survival. Existing literature underscores the interplay between local radiation effects and systemic immune dynamics, highlighting the ability of novel radiotherapies to reshape the tumor immune milieu, reprogram immune cell behaviors, and induce immunogenic cell death. Recent data indicate these modalities not only improve precision and reduce toxicities but also act as potent immunomodulators, yet their full capacity remains under investigation. Growing interest centers around how changes to the tumor immune microenvironment translate into sustained radiosensitization or, conversely, emergent resistance, with gaps remaining in mechanistic clarity, optimal combinations, and patient selection.This Research Topic aims to delineate the multifaceted interactions between novel radiotherapy strategies and tumor immunity, fostering cross-disciplinary discourse and innovation. The primary objectives are to illuminate the immunologic sequelae of new radiation techniques, elucidate immune-primed pathways underpinning radiosensitization, and uncover robust strategies to counteract radioresistance by targeting the immune system. Key questions include: How do specific radiotherapy techniques modulate anti-tumor immune responses? What immune pathways can be effectively leveraged to potentiate radiotherapy outcomes? Which clinical or molecular markers predict successful radiosensitization or emerging resistance following immunomodulatory radiation?The scope of this Research Topic encompasses fundamental, translational, and clinical studies focused on the synergy between emerging radiotherapy techniques and tumor immune modulation. Submissions may address, but are not limited to, mechanistic investigations, therapeutic strategies, and clinical evaluations. To gather further insights in these areas, we welcome articles addressing, but not limited to, the following themes:o Mechanisms by which novel radiotherapy (e.g., FLASH, particle, or stereotactic regimens) modulates tumor immune microenvironments.o Development and assessment of radiosensitizers that target immune pathways or the tumor-immune interface.o Approaches to overcoming radioresistance via immune checkpoint blockade, cytokine modulation, or engineered immune cells.o Clinical trial outcomes and real-world data on combining novel radiotherapy with immunotherapy or targeted agents.o Characterization of immune landscape alterations following novel radiation exposure.o Identification and validation of predictive biomarkers for radiosensitization or radioresistance in immune-modulated radiotherapy contexts. Topic editors: Hong-Shuai Li, Yongjie Xie, Xiaozhou Yu, Xingchen Peng Source: https://www.frontiersin.org/research-topics/78998/novel-radiotherapy-and-tumor-immunity-from-mechanisms-of-radiosensitization-to-overcoming-radioresistance