This study showed that tDC therapy in a preclinical model of MI was potentially translatable into an antiremodeling therapy for ischemic tissue repair.

Dendritic cells (DCs) are increasingly used as adjuvants for vaccination strategies; however, there has been very little development in DC vaccines for patients with hepatocellular carcinoma (HCC). In this study, we assessed the safety, feasibility and efficacy of a multiple tumor-associated antigen (TAA)-pulsed DC vaccine in 5 patients with advanced HCC. DCs were generated by culturing blood monocytes in the presence of granulocyte macrophage-colony stimulating factor and interleukin-4 for 5 days. The DC vaccine was prepared by pulsing DCs with cytoplasmic transduction peptide-attached α-fetoprotein, glypican-3 and MAGE-1 recombinant fusion proteins and cultivating them in the presence of maturation cocktail. DCs were injected subcutaneously near the inguinal lymph nodes, followed by topical application of toll-like receptor-7 agonist around the injection site. We showed that our DC vaccine was safe and well-tolerated over 6 vaccinations in 5 patients. All 5 patients showed T cell responses against TAAs. Clinical benefit was observed in one of the 5 patients. In conclusion, the feasibility, safety and immune activity of DCs pulsed with TAAs were confirmed in HCC patients. However, clinical response was detected only in one patient. Future trials may consider applying this therapy in a less advanced stage to obtain better clinical responses.

Dendritic cells (DCs) are the most potent professional antigen presenting cells and inducers of T cell-mediated immunity. However, few specific markers of mature DCs (mDC) have been reported. A previous microarray analysis revealed expression of mDC-specific genes and identified Rsad2 (radical S-adenosyl methionine domain containing 2) as a candidate specific marker for DC maturation. Mouse bone marrow-derived DCs were transfected with Rsad2 siRNA and examined by flow cytometry, ELISA, western, and confocal microscopy. C57BL/6 mice received intravenously B16F10 cells to establish a pulmonary metastasis model. Tumor-bearing mice then received subcutaneously two injections of mDCs or Rsad2 knockdown DCs. The cytotoxic T lymphocyte (CTL) population was examined from splenocytes of DC-vaccinated mice by flow cytometry. Rsad2 was induced at high levels in LPS-stimulated mDCs and mDC function was markedly attenuated under conditions of Rsad2 knockdown. Moreover, Rsad2 was necessary for mDC maturation via the IRF7-mediated signaling pathway. The importance of Rsad2 was confirmed in an Rsad2 knockdown lung metastasis mouse model in which mDCs lost their antitumor efficacy. Data on the CTL population further supported the results as above. Taken together, Rsad2 was an obvious and specific marker necessary for DC maturation and these findings will be clearly helpful for further understanding of DC biology.

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Taken together, these results show for the first time that myosin-pulsed tDCs ameliorate EAM, and that this occurs most likely via the induction of antigen-specific Treg cells.