Tumor immunotherapy by epicutaneous immunization requires Langerhans cells
Tumor immunotherapy by epicutaneous immunization requires Langerhans cells
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DOI：
10.4049/jimmunol.180.3.1991
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发表时间：
2008-02-01
影响因子：
4.4
通讯作者：
Ronchese, Franca
中科院分区：
文献类型：
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作者：
Stoitzner, Patrizia;Green, Laura K.;Ronchese, Franca
朗格汉斯细胞 (LC) 在诱导皮肤免疫反应中的作用尚未得到最终证实。我们使用 OVA 蛋白进行皮肤免疫来诱导针对表达 OVA 的黑色素瘤细胞的免疫反应。注射OVA特异性CD8+T细胞并在屏障破坏的皮肤上进行OVA免疫的小鼠血液中CD8+T细胞的数量增加，这些细胞产生IFN-γ并杀死靶细胞。这些小鼠在用 OVA 二次免疫后产生加速的细胞毒性反应。在屏障破坏的皮肤上使用 OVA 进行预防性或治疗性免疫可抑制 B16.OVA 肿瘤的生长。 LC在免疫过程中发挥着关键作用，因为皮肤免疫时LC的消耗会显着降低肿瘤保护作用。局部应用的Ag通过引流淋巴结中的皮肤源性LC呈递给CD8(+)T细胞。因此，体内肿瘤抗原靶向LC是肿瘤免疫治疗的有效策略。
A role for Langerhans cells (LC) in the induction of immune responses in the skin has yet to be conclusively demonstrated. We used skin immunization with OVA protein to induce immune responses against OVA-expressing melanoma cells. Mice injected with OVA-specific CD8(+) T cells and immunized with OVA onto barrier-disrupted skin had increased numbers of CD8(+) T cells in the blood that produced IFN-gamma and killed target cells. These mice generated accelerated cytotoxic responses after secondary immunization with OVA. Prophylactic or therapeutic immunization with OVA onto barrier-disrupted skin inhibited the growth of B16.OVA tumors. LC played a critical role in the immunization process because depletion of LC at the time of skin immunization dramatically reduced the tumor-protective effect. The topically applied Ag was presented by skin-derived LC in draining lymph nodes to CD8(+) T cells. Thus, targeting of tumor Ags to LC in vivo is an effective strategy for tumor immunotherapy.