fig1

Figure 1. Schematic illustration demonstrating the multifactorial mechanisms of action of Y-90 radioembolization. (A) Direct cytotoxicity: Intra-arterially delivered Y-90-labeled microspheres preferentially lodge within tumor arterioles, emitting β-radiation that induces double-stranded DNA breaks, leading to apoptosis and mitotic catastrophe; (B) Vascular injury: Radiation-induced endothelial damage disrupts the tumor’s fragile neovasculature, resulting in ischemia, hypoxia, and progressive tumor necrosis; (C) Immunogenic modulation of the tumor microenvironment: Y-90 radiation promotes immunogenic cell death, release of DAMPs, and upregulation of interferon signaling and antigen presentation, facilitating immune cell infiltration and conversion of immunologically “cold” tumors into “hot” tumors. These effects provide a biologic rationale for combining Y-90 radioembolization with systemic therapies, including immune checkpoint inhibitors. Created in BioRender. D, M. (2026) https://BioRender.com/37vhiax CTL: Cytotoxic T lymphocyte; APC: antigen-presenting cell; DAMP: damage-associated molecular pattern; RT: radiation therapy; IFN: interferon; MHC: major histocompatibility complex.