Implantable Immunostimulant Microneedle Patch for Post-Surgical Prevention of Cancer Recurrence and Distant Tumor Inhibition.

Cancer recurrence after surgical resection remains a grand challenge in achieving long-term eradication. Here, we develop a biocompatible and implantable immunostimulant microneedle patch designed to suppress local tumor recurrence after surgery. The patch, fabricated using methacrylate-modified hyaluronic acid, incorporates 2'3'-cGAMP, a STING agonist, and IL-2, a cytokine approved for clinical cancer immunotherapy that expands T cells. The patch enables controlled release of cGAMP to induce dendritic cell maturation, antitumor macrophage polarization (M1 macrophage), and T cell priming and activation. Simultaneously, localized IL-2 activates CD8+ T cells and recruits immune cells to the tumor microenvironment. When combined with an anti-CTLA-4 antibody, an immune checkpoint blockade, the hybrid microneedle patch significantly reduces Treg cells at the surgery sites, enhancing immune responses and effectively inhibiting the progression of distant tumors in both prophylactic and therapeutic models. Compared with traditional postsurgical chemotherapy and radiotherapy, this patch-mediated immunotherapy demonstrates superior efficacy in mitigating tumor relapse while offering higher biocompatibility. Our findings suggest that this immunotherapeutic patch has potential as a translational tool to prevent cancer recurrence in patients with resectable tumors.