Synergizing Radiotherapy with Immunotherapy and Integrative Medicine: Mechanisms, Clinical Translation, and the Role of Acupuncture

Radiation therapy (RT) has historically served as a fundamental method for achieving local tumor control. Recently, a paradigm shift has emerged: RT is now increasingly appreciated for its role as a potent systemic immunomodulator against tumors. Through the induction of immunogenic cell death (ICD) and modulation of the tumor microenvironment (TME), RT is capable of converting treated tumors into in situ vaccines. Nevertheless, this immune-stimulating effect is frequently limited by the concurrent activation of immunosuppressive mechanisms. To address this, combining RT with immunotherapy (IT)—especially immune checkpoint inhibitors (ICIs)—provides a strategic avenue, as RT can trigger an immune response that IT can then enhance and prolong. Furthermore, integrative strategies such as acupuncture, which function as a potential adjunct modulator of the neuro-endocrine-immune network, are demonstrating promise in enhancing the efficacy of radioimmunotherapy and mitigating treatment-related toxicities. This review seeks to explore the mechanistic underpinnings of this synergy, summarize essential clinical evidence, and discuss key factors as well as ongoing challenges in optimizing this innovative combination treatment approach, while also evaluating the prospects of incorporating integrative modalities like acupuncture.