Integrating Radiosensitivity Index and Immune Ecosystems for Prognostic Stratification in Rhabdomyosarcoma: A Preliminary Analysis

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the pediatric population, with fusion-negative RMS (FN-RMS) being the most common histology. Currently, prognostic indicators of treatment response including radiotherapy (RT) are lacking. The radiosensitivity index (RSI) has been developed using individual tumour genomics as a predictor for clinical outcome in RT-treated patients in several cohorts. Similarly, the identification of the composition of the immune compartment in the tumor microenvironment has been shown to be associated with prognosis in other histologies. In this study, we sought to explore the use of RSI and immune classification in stratifying FN-RMS patients according to survival. RSI was confirmed to be significantly associated with patient survival, as well as the macrophage presence in the tumor microenvironment. Thus, we sought to explore the effects of irradiated FN-RMS on macrophages in vitro. Intriguingly, RT appears to similarly polarize macrophages. However, the migration potential appears to be hindered. In conclusion, RSI and macrophage presence in the tumor microenvironment are significantly associated with survival in FN-RMS, with RT appearing to modulate macrophage function and migration.