Improved efficacy of dendritic cell-based immunotherapy by cutaneous laser illumination.
Improved efficacy of dendritic cell-based immunotherapy by cutaneous laser illumination.
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DOI：
10.1158/1078-0432.ccr-11-2654
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发表时间：
2012-04-15
期刊：
影响因子：
--
通讯作者：
Wu MX
中科院分区：
文献类型：
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作者：
Chen X;Zeng Q;Wu MX
目前的研究表明，一种方便的基于激光的方法可以增强 DC 迁移，从而改善小鼠模型中基于 DC 的免疫治疗。通过整体免疫组织化学、透射电子显微镜和流式细胞术测定激光照射对真皮组织微环境和皮内注射后 DC 迁移的影响。我们还通过流式细胞术研究了细胞毒性T淋巴细胞（CTL）的体内扩增，通过体外CTL测定研究了CTL活性，以及在预防性和治疗性肿瘤模型中皮肤激光照射后DC免疫的抗肿瘤功效。研究发现，激光照射会显着扩大淋巴周围基底膜的穿孔，扰乱胶原纤维并破坏真皮中的细胞与基质的相互作用。真皮组织微环境的改变使得皮内注射的 DC 能够更有效地从真皮迁移到引流淋巴结 (dLN)。与注射到假处理皮肤的 DC 相比，激光照射还轻微但显着地增强了注射到皮肤的 DC 上共刺激分子 CD80 和 MHC I 的表达。结果，与对照组相比，激光治疗组获得了更剧烈的肿瘤特异性 IFN-γ+CD8+ T 淋巴细胞扩增，并且针对 4T1 的 CTL 活性增强，但不相关肿瘤细胞的活性并未增强。激光增强 DC 免疫还完全消除了预防性肿瘤模型中 4T1 肿瘤和 B16F10 黑色素瘤的早期生长，并显着延长了治疗性肿瘤模型中 4T1 切除小鼠的生存期。这些数据表明一种简单、安全、基于激光的方法可以显着增强基于 DC 的免疫治疗。
The present investigation demonstrates a convenient laser-based approach to enhance DC migration resulting in improved DC-based immunotherapy in murine models. Influence of laser illumination on dermal tissue microenvironment and migration of DCs following intradermal injection were determined by whole-mount immunohistochemistry, transmission electron microscope, and flow cytometry. We also investigated in vivo expansion of cytotoxic T lymphocytes (CTLs) by flow cytometry, CTL activity by in vitro CTL assay, and anti-tumor efficacy of DC immunization following cutaneous laser illumination in both preventive and therapeutic tumor models. Laser illumination was found to significantly enlarge perforations in the peri-lymphatic basement membrane, disarray collagen fibers and disrupt cell-matrix interactions in the dermis. The altered dermal tissue microenvironment permitted more efficient migration of intradermally injected DCs from the dermis to the draining lymph nodes (dLNs). Laser illumination also slightly but significantly enhanced the expression of costimulatory molecule CD80 and MHC I on DCs injected into the skin, when compared to those DCs administered into sham-treated skin. As a result, more vigorous expansion of tumor-specific IFN-γ+CD8+ T lymphocytes and enhanced CTL activity against 4T1 but not irrelevant tumor cells were obtained in the laser-treated group over the control group. Laser-augmented DC immunization also completely abrogated early growth of 4T1 tumor and B16F10 melanoma in preventive tumor models and significantly extended the survival of 4T1-resected mice in a therapeutic tumor model. These data suggest a simple, safe, laser-based approach to significantly enhance DC-based immunotherapy.