Beyond local control: radiotherapy-immunotherapy combinations from in situ vaccination to systemic immune remodeling.

Optimal radioimmunotherapy strategies require balancing local tumor control with systemic immune activation, with some combinations improving survival in specific cancer types.

• Why it matters: Understanding how radiotherapy remodels the tumor immune microenvironment and triggers immunosuppression is crucial to overcoming limited systemic control and improving patient outcomes.
• What they did: The authors analyze preclinical mechanisms and clinical evidence, examining radiation dose, fractionation, and delivery techniques, and their effects on immune modulation across different cancer settings.
• The result: Effective combinations, such as durvalumab after chemoradiotherapy and SBRT with PD-(L)1 blockade, show benefits in certain contexts, while low-dose RT and spatial strategies offer new solutions to reverse immune exclusion, advancing toward personalized, immune-guided radiotherapy.