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首页> 外文期刊>Journal of dermatological science >Immunohistological analysis of peptide-induced delayed-type hypersensitivity in advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination.
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Immunohistological analysis of peptide-induced delayed-type hypersensitivity in advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination.

机译：晚期黑素瘤患者接受黑素瘤抗原脉冲成熟单核细胞衍生的树突状细胞疫苗治疗后，肽诱导的迟发型超敏反应的免疫组织学分析。

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BACKGROUND: In melanoma patients vaccinated with monocyte-derived melanoma peptide-pulsed dendritic cells (DC), the delayed-type hypersensitivity (DTH) reactions have been examined as a surrogate marker to determine if acquired immunity is induced by DC vaccination. To date, however, only limited information has been reported as for histopathological analyses of DTH. OBJECTIVE: To evaluate tumor-specific immunomonitoring histopathologically after DC vaccination in melanoma patients. METHODS: Seven patients previously vaccinated with monocyte-derived melanoma peptide-pulsed DCs were challenged with recall antigenic peptide injection in the skin of the forearm. Using immunohistochemical techniques, the presence of immune cells and the expression of CD4, CD8, interleukin (IL)-2, IL-4, IL-10, Foxp3, CD1a, CD1d, and interferon (IFN)-gamma was investigated at the site of injection where a DTH reaction developed. RESULTS: Strong DTH reactions from infiltrated erythema to bullae formation were detected in all 7 cases. Biopsies taken from the DTH site revealed heavy infiltration of mononuclear cells and eosinophils in the dermis and subcutaneous tissue. Cells staining positively for CD4, CD8, IL-2, IL-4, Foxp3, CD1d, and IFN-gamma were increased at the site 48h after antigen injection in all cases. Cells positive for IL-10 were never found in any patient. Regulatory T cells appeared 6h after injection and reached their maximum at day 7. CONCLUSIONS: The significant induction of CD8(+)T cells as well as both Th1 and Th2-type cells at the site of DTH suggests that effective antigen presentation leading to anti-tumor immune responses has taken place. Inhibitory mechanisms may also develop as the disappearance of the DTH response could be related to an increase in Foxp3+ cells.
机译：背景：在接种了单核细胞衍生的黑色素瘤肽脉冲树突状细胞（DC）的黑色素瘤患者中，已检查了迟发型超敏反应（DTH）反应作为替代标志物，以确定DC疫苗是否诱导获得性免疫。然而，迄今为止，关于DTH的组织病理学分析仅报道了有限的信息。目的：评估黑色素瘤患者接种DC疫苗后的肿瘤特异性免疫组织学监测。方法：7名先前曾接种过单核细胞源性黑色素瘤肽脉冲DC的患者，接受了在前臂皮肤中注射抗原肽的攻击。使用免疫组织化学技术，在现场研究了免疫细胞的存在以及CD4，CD8，白介素（IL）-2，IL-4，IL-10，Foxp3，CD1a，CD1d和干扰素（IFN）-γ的表达发生DTH反应的注射剂。结果：在所有7例患者中均检测到从渗透性红斑到大疱形成的强烈DTH反应。取自DTH部位的活检显示真皮和皮下组织中单核细胞和嗜酸性粒细胞大量浸润。在所有情况下，抗原注射后48h，CD4，CD8，IL-2，IL-4，Foxp3，CD1d和IFN-γ阳性染色的细胞均增加。在任何患者中都从未发现过IL-10阳性的细胞。调节性T细胞在注射后6h出现，并在第7天达到最大。结论：在DTH部位，CD8（+）T细胞以及Th1和Th2型细胞的显着诱导表明有效的抗原呈递可导致抗肿瘤免疫反应已经发生。由于DTH反应的消失可能与Foxp3 +细胞的增加有关，因此也可能形成抑制机制。

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