Ji Jie, Fan Zhixia, Zhou Feifan, Wang Xiaojie, Shi Lei, Zhang Haiyan, Wang Peiru, Yang Degang, Zhang Linglin, Chen Wei R, Wang Xiuli
Department of Photomedicine, Shanghai Skin Disease Hospital, Shanghai 200443, China.
Biophotonics Research Laboratory, Center for Interdisciplinary Biomedical Education and Research, University of Central Oklahoma, Edmond, OK 73034, USA.
Oncotarget. 2015 Jul 10;6(19):17135-46. doi: 10.18632/oncotarget.3529.
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-γ 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.
基于树突状细胞（DC）的疫苗已成为一种有前景的癌症免疫疗法。然而，迄今为止，大多数DC疫苗在癌症治疗中仅取得了有限的成功。光动力疗法（PDT）是一种成熟的癌症治疗策略，可引起免疫原性凋亡以诱导有效的抗肿瘤免疫反应。在本研究中，我们使用由5-氨基乙酰丙酸（ALA）介导的PDT诱导的免疫原性凋亡肿瘤细胞开发了一种基于DC的癌症疫苗。使用电子显微镜、流式细胞术和酶联免疫吸附测定法评估了经PDT处理的凋亡细胞诱导的DC成熟情况。用小鼠模型测试了ALA-PDT-DC疫苗的抗肿瘤免疫力。我们观察到经ALA-PDT处理的肿瘤细胞增强了DC的成熟，包括形态成熟（树突增大和溶酶体增加）、表型成熟（MHC-II、DC80和CD86表面表达上调）和功能成熟（分泌IFN-γ和IL-12以及诱导T细胞增殖的能力增强）。最有趣的是，PDT诱导的凋亡肿瘤细胞比PDT处理或冻融处理的坏死肿瘤细胞更能增强DC的成熟。由凋亡细胞介导的ALA-PDT-DC疫苗为小鼠提供了抗肿瘤保护，远比从冻融处理的肿瘤细胞获得的DC疫苗更强。我们的结果表明，免疫原性凋亡肿瘤细胞在增强基于DC的癌症疫苗方面可能更有效，这可能会改善PDT-DC疫苗的临床应用。
