Journal
ONCOTARGET
Volume 6, Issue 19, Pages 17135-17146Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.3529
Keywords
dendritic cell; photodynamic therapy; immunogenic apoptosis; 5-aminolevulinic acid; PDT-DC vaccine
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Funding
- National Natural Science Foundation of China [81272990, 81472538, 81472796]
- Basic Research Project of Science and Technology of Shanghai [13JC1405101]
- Advanced Suitable Technology Popularization Project of Shanghai Health System [2013SY007]
- Key Project of Shanghai Municipal Commission of Health and Family Planning [20124034]
- US National Institutes of Health [R21 EB0155091-01]
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Dendritic cell (DC) based vaccines have emerged as a promising immunotherapy for cancers. However, most DC vaccines so far have achieved only limited success in cancer treatment. Photodynamic therapy (PDT), an established cancer treatment strategy, can cause immunogenic apoptosis to induce an effective antitumor immune response. In this study, we developed a DC-based cancer vaccine using immunogenic apoptotic tumor cells induced by 5-aminolevulinic acid (ALA) mediated PDT. The maturation of DCs induced by PDT-treated apoptotic cells was evaluated using electron microscopy, FACS, and ELISA. The anti-tumor immunity of ALA-PDT-DC vaccine was tested with a mouse model. We observed the maturations of DCs potentiated by ALA-PDT treated tumor cells, including morphology maturation (enlargement of dendrites and increase of lysosomes), phenotypic maturation (upregulation of surface expression of MHC-II, DC80, and CD86), and functional maturation (enhanced capability to secrete IFN-gamma and IL-12, and to induce T cell proliferation). Most interestingly, PDT-induced apoptotic tumor cells are more capable of potentiating maturation of DCs than PDT-treated or freeze/thaw treated necrotic tumor cells. ALA-PDT-DC vaccine mediated by apoptotic cells provided protection against tumors in mice, far stronger than that of DC vaccine obtained from freeze/thaw treated tumor cells. Our results indicate that immunogenic apoptotic tumor cells can be more effective in enhancing a DC-based cancer vaccine, which could improve the clinical application of PDT-DC vaccines.
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