An Integrated Modular Vaccination System for Spatiotemporally Separated Perioperative Cancer Immunotherapy

The perioperative period is crucial for determining postoperative tumor recurrence and metastasis. Various factors in postoperative lesions can diminish the therapeutic effect of conventional chemoradiotherapy, while emerging immunotherapy is restricted. The combination use of inflammatory inhibitors during treatment is also controversial. Here, a modular microneedle prepared from engineered keratin proteins is reported, which spatially and temporally differentiates the microenvironment of immune cell activation required for immunotherapy from that of wound healing. The recombinant keratin-84-T-based needle root layer, mainly retained in the epidermis, facilitated dendritic cell recruitment to achieve maximum antigen presentation of loaded vaccines. Meanwhile, the recombinant keratin-81-1Aα-based needle tip layer, located within the dermis, rapidly mitigated inflammatory responses while promoting tissue repair and regeneration. Unlike simply mixing immunotherapy and wound treatment, this spatiotemporal segmentation approach maximized the efficacy of immune therapeutics while promoting wound healing, making it suitable for application throughout the perioperative period.