Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Department of Medical Oncology, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands.
Cell Rep. 2020 Jan 28;30(4):1027-1038.e4. doi: 10.1016/j.celrep.2019.12.096.
Plasmacytoid dendritic cells (pDCs) and type 2 conventional dendritic cells (cDC2s) are currently under evaluation for use in cancer vaccines. Although both DC subsets can activate adaptive and innate lymphocytes, their capacity to recruit such cells is rarely considered. Here, we show that pDCs and cDC2s display a striking difference in chemokine secretion, which correlates with the recruitment of distinct types of immune effector cells. Activated pDCs express high levels of CXCR3 ligands and attract more CD8 T cells, CD56 T cells, and γδ T cells in vitro, compared to cDC2s. Skin from melanoma patients shows an influx of immune effector cells following intradermal vaccination with pDCs or cDC2s, with pDCs inducing the strongest influx of lymphocytes known to possess cytolytic activity. These findings suggest that combining both DC subsets could unite the preferred chemoattractive properties of pDCs with the superior T cell priming properties of cDC2s to ultimately enhance vaccine efficacy.
浆细胞样树突状细胞（pDCs）和 2 型传统树突状细胞（cDC2s）目前正在评估用于癌症疫苗。尽管这两个 DC 亚群都可以激活适应性和先天淋巴细胞，但它们招募这些细胞的能力很少被考虑。在这里，我们表明 pDCs 和 cDC2s 在趋化因子分泌方面表现出显著差异，这与招募不同类型的免疫效应细胞相关。与 cDC2s 相比，激活的 pDCs 表达高水平的 CXCR3 配体，并在体外吸引更多的 CD8 T 细胞、CD56 T 细胞和 γδ T 细胞。来自黑色素瘤患者的皮肤在接受 pDCs 或 cDC2s 的皮内疫苗接种后，会有免疫效应细胞涌入，其中 pDCs 诱导已知具有细胞毒性活性的淋巴细胞最强涌入。这些发现表明，结合这两种 DC 亚群可以将 pDCs 的首选趋化吸引力与 cDC2s 的优异 T 细胞启动特性结合起来，最终增强疫苗效力。
