PM@DCm nanohybrid-mediated pleiotropic antigen presentation for enhanced melanoma immunotherapy

Abstract

Melanoma, an aggressive cancer with poor prognosis, benefits only minimally from the current immunotherapies. To address these therapeutic shortcomings, achieving efficient antigen presentation is pivotal for robust tumor-specific T-cell activation and durable antitumor immunity. Here, a multifunctional nanohybrid (denoted as PM@DCm) with activated DC membrane-coated, platinum-embedded, hollow manganese-based nanohybrid is developed, which can effectively proceed antigens presentation. The core of multispiked platinum-manganese oxide (termed as Pt@MnO₂) functions dually as a Stimulator of Interferon Genes (STING) agonist and an inducer of immunogenic cell death (ICD) in response to the tumor microenvironment, triggering inflammatory cytokine and actionable tumor antigens release. These events facilitate in-situ DC maturation, improving antigen uptake and presentation to T cells. Simultaneously, the DC-mimetic structure of PM@DCm retains critical costimulatory markers, MHC class I antigen complexes, and chemokine receptors, effectively simulating the functionality of mature DCs. This dual mechanism ensures robust pleiotropic antigen cross-presentation and cytotoxic T-cell priming. As a result, this PM@DCm nanohybrid significantly suppresses tumor growth and metastasis, elicits robust antitumor immunity, and shows strong prophylactic potential. This novel strategy leverages the synergy between mimicking mature DCs and promoting in-stiu DC maturation, delivering pleiotropic antigen presentation for enhanced melanoma immunotherapy.