Gerlini Gianni, Urso Carmelo, Mariotti Giulia, Di Gennaro Paola, Palli Domenico, Brandani Paola, Salvadori Adriana, Pimpinelli Nicola, Reali Umberto Maria, Borgognoni Lorenzo
Plastic Surgery Unit - Regional Melanoma Referral Center, Santa Maria Annunziata Hospital, Florence, Italy.
Clin Immunol. 2007 Nov;125(2):184-93. doi: 10.1016/j.clim.2007.07.018. Epub 2007 Sep 10.
Plasmacytoid dendritic cells (pDC) represent the main source of interferon-alpha, a cytokine with antitumor activity. However, in vitro studies point to pDC as a key subset for induction of tolerance. Herein, we investigated pDC in sentinel lymph nodes (SLN) of melanoma patients. We report that pDC were constantly found in SLN and represented, with Langerhans cells, the most frequent dendritic cell subset. Their frequency in positive (with metastasis) SLN was significantly higher than in negative (without metastasis) SLN. PDC were observed in the T cell-rich areas of lymph nodes, particularly around high endothelial venules and, in metastatic nodes, they accumulated in close vicinity with melanoma nests. Finally, pDC capability to produce interferon-alpha in situ was impaired. Consistently, pDC expressed CD86, but neither CD80 nor CD83, suggesting a not complete activation in melanoma-draining lymph nodes. These results are consistent with the hypothesis of a tolerogenic role played by pDC in tumor immunology.
浆细胞样树突状细胞(pDC)是具有抗肿瘤活性的细胞因子——α干扰素的主要来源。然而,体外研究表明pDC是诱导免疫耐受的关键亚群。在此,我们研究了黑色素瘤患者前哨淋巴结(SLN)中的pDC。我们报告称,在SLN中经常发现pDC,并且与朗格汉斯细胞一起,是最常见的树突状细胞亚群。它们在阳性(有转移)SLN中的频率显著高于阴性(无转移)SLN。在淋巴结富含T细胞的区域观察到pDC,特别是在高内皮小静脉周围,并且在转移淋巴结中,它们聚集在黑色素瘤巢附近。最后,pDC原位产生α干扰素的能力受损。一致地,pDC表达CD86,但不表达CD80和CD83,这表明在引流黑色素瘤的淋巴结中pDC没有完全激活。这些结果与pDC在肿瘤免疫学中发挥致耐受性作用的假设一致。