Mechanoimmune-Driven\nBackpack Sustains Dendritic Cell\nMaturation for Synergistic Tumor Radiotherapy

Cell\nbackpacks present significant potential in both therapeutic\nand diagnostic applications, making it essential to further explore\ntheir interactions with host cells. Current evidence indicates that\nbackpacks can induce sustained immune responses. Our original objective\nwas to incorporate a model antigen into the backpacks to promote dendritic\ncell maturation and facilitate antigen presentation, thereby inducing\nimmune responses. However, we unexpectedly discovered that both antigen-loaded\nbackpacks and empty backpacks demonstrated comparable abilities to\ninduce dendritic cell maturation, resulting in nearly identical potency\nin T-cell proliferation. Our mechanistic studies suggest that the\nattachment of backpacks induces mechanical forces on dendritic cells\nvia opening the PIEZO1 mechanical ion channel. This interaction leads\nto the remodeling of the intracellular cytoskeleton and facilitates\nthe production of type I interferons by dendritic cells. Consequently,\nthe mechano-immune-driven dendritic cell backpacks, when combined\nwith radiotherapy, induce a robust antitumor effect. This research\npresents an avenue for leveraging mechanotransduction to enhance combination\nimmunotherapeutic strategies, potentially leading to groundbreaking\nadvancements in the field.