Multiple clinical trials have shown an overall improved response rate in cancers by combining radiotherapy (RT) with immunotherapy (IO), however, treatment rates remain low and unpredictable. The suboptimal outcomes are largely due to the lack of knowledge of the underlying immunomodulation effect and an effective treatment-response biomarker. Previous studies using tissue-based assays like multiplexed immunofluorescence (mIF) have demonstrated that cellular spatial organization within the tumor microenvironment represents a critical factor influencing anti-tumor immunity. Hence, we sought to characterize the in-situ molecular immune response of RT-treated cancer tissues by using multiple spatial and immunology technologies, to advance our understanding of RT-induced immunomodulation effect and its synergistic benefits with IO.
