Institute of Immunology, Johannes Gutenberg University Medical Center, Mainz, Germany.
J Invest Dermatol. 2011 Jan;131(1):211-9. doi: 10.1038/jid.2010.254. Epub 2010 Aug 26.
Immunologic approaches to combat cancer aim at the induction of tumor-reactive immune responses to achieve long-term protection. In this context, we recently developed a transcutaneous immunization (TCI) method using the Toll-like receptor (TLR) 7 agonist imiquimod and a peptide epitope. Application onto intact skin induces potent cytotoxic T lymphocyte (CTL) responses and protection against transplanted tumors. The purpose of this study was to explore the effects of UV irradiation on imiquimod-based TCI. Here we show that skin exposure to low-dose UV light before TCI with imiquimod strongly boosts specific CTL responses leading to memory formation and enhanced tumor protection. Toward the mechanisms, we show that the activation of bone-marrow-derived dermal dendritic cells (DCs), but not Langerin-expressing DCs, is responsible for enhanced CTL activation. We describe an optimized TCI method that mediates enhanced CTL and antitumor responses by a DC- and TLR-dependent mechanism. These data may provide the basis for the future development of advanced vaccination protocols against tumors and persistent virus infections.
免疫疗法旨在诱导针对肿瘤的免疫反应，以实现长期保护。在这方面，我们最近开发了一种经皮免疫（TCI）方法，该方法使用 Toll 样受体（TLR）7 激动剂咪喹莫特和肽表位。将其应用于完整皮肤可诱导强烈的细胞毒性 T 淋巴细胞（CTL）反应，并对移植瘤起到保护作用。本研究旨在探讨紫外线照射对咪喹莫特为基础的 TCI 的影响。结果表明，TCI 前用低剂量紫外线照射皮肤可强烈增强特异性 CTL 反应，从而形成记忆并增强肿瘤保护。在机制方面，我们发现骨髓来源的真皮树突状细胞（DC）的激活而不是朗格汉斯细胞表达的 DC 激活，是增强 CTL 激活的原因。我们描述了一种优化的 TCI 方法，该方法通过 DC 和 TLR 依赖性机制介导增强的 CTL 和抗肿瘤反应。这些数据可能为未来针对肿瘤和持续性病毒感染的先进疫苗接种方案的发展提供基础。
