Edele Fanny, Dudda Jan C, Bachtanian Eva, Jakob Thilo, Pircher Hanspeter, Martin Stefan F
Allergy Research Group, Department of Dermatology, Medical Center - University of Freiburg, Freiburg, Germany.
Institute for Medical Microbiology and Hygiene, Medical Center - University of Freiburg, Freiburg, Germany.
PLoS One. 2014 Aug 14;9(8):e105266. doi: 10.1371/journal.pone.0105266. eCollection 2014.
Dendritic cells (DC) presenting tumor antigens are crucial to induce potent T cell-mediated anti-tumor immune responses. Therefore DC-based cancer vaccines have been established for therapy, however clinical outcomes are often poor and need improvement. Using a mouse model of B16 melanoma, we found that the route of preventive DC vaccination critically determined tumor control. While repeated DC vaccination did not show an impact of the route of DC application on the prevention of tumor growth, a single DC vaccination revealed that both the imprinting of skin homing receptors and an enhanced proliferation state of effector T cells was seen only upon intracutaneous but not intravenous or intraperitoneal immunization. Tumor growth was prevented only by intracutaneous DC vaccination. Our results indicate that under suboptimal conditions the route of DC vaccination crucially determines the efficiency of tumor defense. DC-based strategies for immunotherapy of cancer should take into account the immunization route in order to optimize tissue targeting of tumor antigen specific T cells.
呈递肿瘤抗原的树突状细胞（DC）对于诱导有效的T细胞介导的抗肿瘤免疫反应至关重要。因此，基于DC的癌症疫苗已被用于治疗，但临床结果往往不佳，需要改进。利用B16黑色素瘤小鼠模型，我们发现预防性DC疫苗接种的途径对肿瘤控制起着关键作用。虽然重复进行DC疫苗接种未显示DC接种途径对肿瘤生长预防有影响，但单次DC疫苗接种显示，只有在皮内接种而非静脉或腹腔免疫时，才会出现皮肤归巢受体的印记以及效应T细胞增殖状态的增强。只有皮内DC疫苗接种才能预防肿瘤生长。我们的结果表明，在次优条件下，DC疫苗接种途径对肿瘤防御效率起着关键作用。基于DC的癌症免疫治疗策略应考虑免疫接种途径，以优化肿瘤抗原特异性T细胞的组织靶向。
