Romoli Maria Raffaella, Di Gennaro Paola, Gerlini Gianni, Sestini Serena, Brandani Paola, Ferrone Soldano, Borgognoni Lorenzo
Plastic and Reconstructive Surgery Unit, Regional Melanoma Referral Center and Melanoma & Skin Cancer Unit, Tuscan Tumour Institute (ITT) - S.M. Annunziata Hospital, Florence, Italy.
Plastic and Reconstructive Surgery Unit, Regional Melanoma Referral Center and Melanoma & Skin Cancer Unit, Tuscan Tumour Institute (ITT) - S.M. Annunziata Hospital, Florence, Italy; Dept. Surgery and Translational Medicine, Dermatology Section, University of Florence, Florence, Italy.
Cell Immunol. 2017 Oct;320:29-37. doi: 10.1016/j.cellimm.2017.08.007. Epub 2017 Aug 30.
Langerhans cells (LCs) from melanoma patients sentinel lymph nodes (SLN) are poor T cell activators mostly due to an immature immunophenotype. However Antigen Presenting Machinery (APM) role is unknown. We investigated HLA-class I APM components (Delta, LMP-7/10, TAP-1, Calnexin, Tapasin, β2-microglobulin and HLA-A,B,C) in LCs from healthy donors skin and melanoma patients SLN. APM component levels were low in immature epidermal LCs and significantly increased after maturation (p<0.05); their levels were significantly high in SLN LCs (p<0.01). APM component expression correlated with melanoma Breslow's thickness and SLN metastases: HLA-A,B,C level was significantly lower in SLN LCs from thick lesions patients compared with those from thin/intermediate lesions (p<0.05); β2-microglobulin level was significantly higher in positive SLN LCs compared to negative ones (p<0.05). Functionally, SLN LCs did not phagocytose exogenous antigens. These findings extend LCs knowledge indicating that they are not fully impaired by melanoma, contributing to design new LCs-based therapeutic approaches.
黑色素瘤患者前哨淋巴结(SLN)中的朗格汉斯细胞(LC)大多因免疫表型不成熟而成为较差的T细胞激活剂。然而,抗原呈递机制(APM)的作用尚不清楚。我们研究了健康供体皮肤和黑色素瘤患者SLN的LC中HLA-I类APM成分(Delta、LMP-7/10、TAP-1、钙连接蛋白、塔帕辛、β2-微球蛋白和HLA-A、B、C)。未成熟表皮LC中的APM成分水平较低,成熟后显著升高(p<0.05);其水平在SLN的LC中显著较高(p<0.01)。APM成分表达与黑色素瘤的 Breslow厚度和SLN转移相关:与薄/中等厚度病变患者的SLN的LC相比,厚病变患者的SLN的LC中HLA-A、B、C水平显著较低(p<0.05);阳性SLN的LC中β2-微球蛋白水平显著高于阴性SLN的LC(p<0.05)。在功能上,SLN的LC不吞噬外源性抗原。这些发现扩展了对LC的认识,表明它们并未完全被黑色素瘤损害,有助于设计新的基于LC的治疗方法。