FIGURE 1.

TRT and ICI synergize via immune mechanisms. TRT agent binds a tumor cell target receptor, and emitted radiation induces release of tumor-associated antigens and damage-associated molecular patterns (DAMPs), causes DNA damage, and potentially prompts immunogenic cell death. Damaged cytoplasmic DNA stimulates STING, leading to a type I interferon response. Tumor MHC-I expression is increased as is neoantigen display, and stimulated activation of dendritic cells (DCs) correspondingly increases antigen cross-presentation to T cells. The expression of immune checkpoint molecules is modulated, allowing for maintained immune activation with ICI. As a DAMP, calreticulin is newly expressed on the outer membrane of tumor cells undergoing immunogenic cell death ( 18 ), leading to phagocytosis by DCs that is central to their activation ( 7 ). dsDNA = double-stranded DNA; TCR = T-cell receptor. (Created with BioRender.com.)