WITHDRAWN: JUN and ATF3 are deficient in prostate cancer patients and their delivery in vivo via lipid nanoparticles has therapeutic efficacy by enhancing immune surveillance

Immune system perturbation has been revealed as a main contributor to the development of various types of cancer, including prostate cancer (PCa). Lipid nanoparticles (LNPs) have been revealed to induce anti-tumor immunity for hepatocellular carcinoma. Thus, we evaluated the potential of LNPs loaded with immune gene regulons for treating PCa. By using single-cell sequencing data of PCa in the GEO database, we identified that macrophages and T cells were the main cell types of PCa heterogeneity. Furthermore, JUN and ATF3, major genes in T cells and macrophages, were significantly poorly expressed in PCa, which predicted a poor prognosis. LNPs loaded with JUN and ATF3 pDNA slowed the metastatic fate in tumor-bearing mice and reduced secretion of tumor-stimulating factors, as evidenced by accelerated macrophage polarization and increased T-cell infiltration. These findings suggested that the combination of the two via LNPs had efficacy in vivo. LNPs significantly promoted macrophage activity and inhibited the immune evasion of PCa cells in vitro. Collectively, our work identified LNPs loaded with regulons significantly promoted macrophage polarization and T cell activity and enhanced immune surveillance to inhibit PCa progression, gaining insights into the heterogeneity of PCa immune microenvironment and holding promise for optimized PCa treatment using LNPs.