Anti-tumor effects of DNA vaccine targeting human fibroblast activation protein α by producing specific immune responses and altering tumor microenvironment in the 4T1 murine breast cancer model
Anti-tumor effects of DNA vaccine targeting human fibroblast activation protein α by producing specific immune responses and altering tumor microenvironment in the 4T1 murine breast cancer model
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DOI：
10.1007/s00262-016-1827-4
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发表时间：
2016-03
期刊：
影响因子：
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通讯作者：
Q. Xia;Fangfang Zhang;F. Geng;Chenlu Liu;P. Xu;Zhenzhen Lu;Bin Yu;H. Wu;Jiaxin Wu;
中科院分区：
文献类型：
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作者：
Q. Xia;Fangfang Zhang;F. Geng;Chenlu Liu;P. Xu;Zhenzhen Lu;Bin Yu;H. Wu;Jiaxin Wu;
成纤维细胞激活蛋白 α (FAPα) 是一种由癌症相关成纤维细胞 (CAF) 过度表达的肿瘤基质抗原。与肿瘤细胞和肿瘤微环境的免疫抑制成分相比，CAF 在遗传上更加稳定，使其成为癌症免疫治疗的绝佳靶点。 DNA疫苗因其安全性而被广泛应用。为了特异性破坏CAF，我们构建并检测了表达人FAPα的DNA疫苗的免疫原性和抗肿瘤免疫机制。该疫苗通过产生可杀死 CAF 的 FAPα 特异性细胞毒性 T 淋巴细胞反应，成功减少了 4T1 肿瘤的生长，并且表达 FAPα 的 CAF 的减少导致 I 型胶原蛋白和其他有利于肿瘤进展的基质因子的表达显着减弱。基于这些结果，针对人类 FAPα 的 DNA 疫苗可能是一种有吸引力且有效的癌症免疫治疗策略。
Fibroblast activation protein α (FAPα) is a tumor stromal antigen overexpressed by cancer-associated fibroblasts (CAFs). CAFs are genetically more stable compared with the tumor cells and immunosuppressive components of the tumor microenvironment, rendering them excellent targets for cancer immunotherapy. DNA vaccines are widely applied due to their safety. To specifically destroy CAFs, we constructed and examined the immunogenicity and anti-tumor immune mechanism of a DNA vaccine expressing human FAPα. This vaccine successfully reduced 4T1 tumor growth through producing FAPα-specific cytotoxic T lymphocyte responses which could kill CAFs, and the decrease in FAPα-expressing CAFs resulted in markedly attenuated expression of collagen I and other stromal factors that benefit the tumor progression. Based on these results, a DNA vaccine targeting human FAPα may be an attractive and effective cancer immunotherapy strategy.