Immunohistological analysis of peptide-induced delayed-type hypersensitivity in advanced melanoma patients treated with melanoma antigen-pulsed mature monocyte-derived dendritic cell vaccination
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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DOI：
10.1016/j.jdermsci.2008.07.013
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发表时间：
2009-01-01
影响因子：
4.6
通讯作者：
Kishimoto, Saburo
中科院分区：
文献类型：
--
作者：
Nakai, Noriaki;Katoh, Norito;Kishimoto, Saburo
背景：在接受单核细胞来源的黑色素瘤多肽致敏的树突状细胞(DC)免疫的黑色素瘤患者中，迟发型超敏反应(DTH)被检测为替代标志物，以确定DC疫苗是否诱导了获得性免疫。目的：评价黑色素瘤患者DC疫苗免疫后的组织病理学变化。方法：对7例既往接种单核细胞来源的黑色素瘤多肽致敏DC的患者前臂皮肤注射Recall抗原肽进行攻击。采用免疫组织化学方法，观察注射部位免疫细胞的存在及CD4、CD8、IL-2、IL-4、IL-10、Foxp3、CD1a、CD1d和干扰素-γ的表达。DTH部位的活组织检查显示真皮和皮下组织中有大量的单核细胞和嗜酸性粒细胞的渗透。CD4染色阳性的细胞。CD8、IL-2、IL-4、Foxp3。所有病例在注射抗原后48h，CD1d、干扰素-γ均升高。所有患者均未发现IL-10阳性细胞。调节性T细胞在注射后6h出现，7d达高峰。结论：DTH部位CD8(+)T细胞和Th1、Th2细胞均有明显诱导，提示已发生有效的抗肿瘤免疫反应。抑制机制也可能发展，因为DTH反应的消失可能与Foxp3+细胞的增加有关。(C)2008年日本皮肤病研究学会。爱思唯尔爱尔兰有限公司出版。版权所有。
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 48 h after antigen injection in all cases. Cells positive for IL-10 were never found in any patient. Regulatory T cells appeared 6 h 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. (c) 2008 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.