Radiotherapy-induced immunity is real but incomplete: nano-immunoadjuvants as immune amplifiers in radioimmunotherapy

Abstract

Abstract Radiotherapy (RT) can initiate antitumor immunity through immunogenic cell death, tumor-associated antigen release, and innate immune engagement, but these responses are often too weak and transient to achieve durable systemic tumor control. This perspective identifies insufficient immune amplification as a central bottleneck in radioimmunotherapy and positions nano-immunoadjuvant (NIA) as programmable systems that enhance RT-induced immune priming, remodel the suppressive tumor microenvironment, and support adaptive antitumor immunity. Unlike conventional approaches focused mainly on radiosensitization, drug delivery, or immune initiation, we propose a “trigger–amplify–sustain” framework in which RT initiates immunity, NIA amplifies it, and immune checkpoint blockade maintains it. We also discuss key translational challenges, including radiation fractionation, scalable manufacturing, biomarker-guided patient selection, and regulatory evaluation, supporting a shift toward programmable radioimmunotherapy.