Departments of Medical Oncology, VU University Medical Center/Cancer Center Amsterdam, De Boelelaan, Amsterdam, The Netherlands.
Blood. 2011 Sep 1;118(9):2502-10. doi: 10.1182/blood-2011-03-344838. Epub 2011 Jul 12.
To increase (tumor) vaccine efficacy, there is an urgent need for phenotypic and functional characterization of human dendritic cell (DC) subsets residing in lymphoid tissues. In this study we identified and functionally tested 4 human conventional DC (cDC) subsets within skin-draining sentinel lymph nodes (SLNs) from early-stage melanoma patients. These SLNs were all tumor negative and were removed on average 44 days after excision of the primary melanoma. As such, they were considered representative of steady-state conditions. On comparison with skin-migrated cDC, 2 CD1a(+) subsets were identified as most likely skin-derived CD11c(int) Langerhans cells (LC) with intracellular langerin and E-cadherin expression or as CD11c(hi) dermal DCs with variable expression of langerin. Two other CD1a(-) LN-residing cDC subsets were characterized as CD14(-)BDCA3(hi)CD103(-) and CD14(+)BDCA3(lo)CD103(+), respectively. Whereas the CD1a(+) skin-derived subsets displayed greater levels of phenotypic maturation, they were associated with lower levels of inflammatory cytokine release and were inferior in terms of allogeneic T-cell priming and IFNγ induction. Thus, despite their higher maturation state, skin-derived cDCs (and LCs in particular) proved inferior T-cell activators compared with the CD1a(-) cDC subsets residing in melanoma-draining LNs. These observations should be considered in the design of DC-targeting immunotherapies.
为了提高（肿瘤）疫苗的疗效，迫切需要对驻留在淋巴组织中的人类树突状细胞（DC）亚群进行表型和功能特征分析。在这项研究中，我们在早期黑色素瘤患者的皮肤引流前哨淋巴结（SLN）中鉴定并功能测试了 4 种人类常规 DC（cDC）亚群。这些 SLN 均为肿瘤阴性，并且在切除原发性黑色素瘤后平均 44 天被切除。因此，它们被认为代表了稳态条件。与皮肤迁移的 cDC 相比，我们鉴定出 2 个 CD1a(+) 亚群最有可能是具有细胞内 langerin 和 E-钙黏蛋白表达的皮肤来源的 CD11c(int)朗格汉斯细胞（LC），或者是具有可变 langerin 表达的 CD11c(hi)真皮 DC。另外两个 CD1a(-)LN 驻留的 cDC 亚群分别被鉴定为 CD14(-)BDCA3(hi)CD103(-)和 CD14(+)BDCA3(lo)CD103(+)。虽然 CD1a(+)皮肤来源的亚群显示出更高水平的表型成熟，但它们与较低水平的炎症细胞因子释放相关，并且在同种异体 T 细胞启动和 IFNγ诱导方面较差。因此，尽管皮肤来源的 cDC（特别是 LC）具有更高的成熟状态，但与驻留在黑色素瘤引流淋巴结中的 CD1a(-)cDC 亚群相比，它们证明是较差的 T 细胞激活剂。这些观察结果在设计针对 DC 的免疫疗法时应予以考虑。
