Fausch Steven C, Da Silva Diane M, Kast W Martin
Cancer Immunology Program, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, Illinois 60153, USA.
Cancer Res. 2003 Jul 1;63(13):3478-82.
A causal link between cervical cancer and high-risk human papillomaviruses has been established. The virus infects basal cells of the mucosa, where Langerhans cells are the resident antigen-presenting cells. Langerhans cells and dendritic cells, which are targeted by vaccination, internalize similar amounts of human papillomavirus virus-like particles (VLPs), albeit through different uptake mechanisms. VLP uptake by dendritic cells results in activation and cross-presentation of MHC class I-restricted peptides with costimulation to T cells. Conversely, VLP uptake by Langerhans cells leads to cross-presentation in the absence of costimulation. Efficient VLP cross-presentation by Langerhans cells with costimulation can be achieved by addition of CD40 ligand. The lack of a protective immune response after viral contact with Langerhans cells may explain why some women fail to mount an immune response against the virus or why the immune responses that do develop may allow the virus to persist. Because VLPs are currently being tested as a vaccine against cervical cancer, our data are very topical and have implications for optimal vaccination strategies against this disease.
子宫颈癌与高危型人乳头瘤病毒之间的因果联系已得到证实。该病毒感染黏膜的基底细胞，其中朗格汉斯细胞是驻留的抗原呈递细胞。朗格汉斯细胞和树突状细胞是疫苗的作用靶点，它们摄取相似数量的人乳头瘤病毒样颗粒（VLP），尽管摄取机制不同。树突状细胞摄取VLP会导致MHC I类限制性肽的激活和交叉呈递，并伴有对T细胞的共刺激。相反，朗格汉斯细胞摄取VLP会在缺乏共刺激的情况下导致交叉呈递。通过添加CD40配体可实现朗格汉斯细胞在有共刺激情况下高效的VLP交叉呈递。病毒与朗格汉斯细胞接触后缺乏保护性免疫反应，这或许可以解释为什么一些女性无法对该病毒产生免疫反应，或者为什么已产生的免疫反应可能会使病毒持续存在。由于VLP目前正作为子宫颈癌疫苗进行测试，我们的数据具有很强的时效性，对针对该疾病的最佳疫苗接种策略具有重要意义。
