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黑色素瘤患者前哨淋巴结中朗格汉斯细胞的高抗原加工机制成分表达。

High Antigen Processing Machinery component expression in Langerhans cells from melanoma patients' sentinel lymph nodes.

作者信息

Romoli Maria Raffaella, Di Gennaro Paola, Gerlini Gianni, Sestini Serena, Brandani Paola, Ferrone Soldano, Borgognoni Lorenzo

机构信息

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.

出版信息

Cell Immunol. 2017 Oct;320:29-37. doi: 10.1016/j.cellimm.2017.08.007. Epub 2017 Aug 30.

Abstract

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.

摘要

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。

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