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肾移植受者良性、癌前和恶性皮肤病变中的朗格汉斯细胞及维甲酸治疗的效果

Langerhans cells in benign, premalignant and malignant skin lesions of renal transplant recipients and the effect of retinoid therapy.

作者信息

Gibson G E, O'Grady A, Kay E W, Leader M, Murphy G M

机构信息

Department of Dermatology, Beaumont Hospital, Dublin, Ireland.

出版信息

J Eur Acad Dermatol Venereol. 1998 Mar;10(2):130-6.

PMID:9553909
Abstract

BACKGROUND AND DESIGN

Langerhans cells (LC) are a unique population of antigen-presenting cells in the epidermis which may play a role in the defense mechanisms against skin tumors. Renal transplant recipients (RTRs) have a significantly increased incidence of premalignant and malignant skin lesions. Langerhans cells, which are important for local immune surveillance, may be depleted or downregulated in skin neoplasms of RTRs, facilitating their growth. We investigated the Langerhans cell densities in 29 squamous cell carcinomas (SCCs), five basal cell carcinomas (BCCs), four Bowen's disease, eight dysplastic lesions (actinic keratoses), and three viral warts from 15 RTRs and compared these to the Langerhans cell densities in normal control skin. Eleven RTRs were receiving low-dose etretinate as chemoprophylaxis for recurrent skin cancer and the effect of low-dose retinoid therapy on Langerhans cell densities in SCCs from these patients was also assessed. Langerhans cells in frozen tissue sections were stained with the anti-human Leu-6 monoclonal antibody.

RESULTS

There was no significant difference in LC numbers between normal skin from RTRs and normal skin from non-immunosuppressed individuals. There was a statistically significant reduction in LC/mm2 and LC/1000 K (keratinocytes) for SCC, BCC, dysplastic lesions and viral warts compared with normal skin (P < 0.001, P < 0.01, P < 0.001, P < 0.05, respectively). There was a trend for an increase in Langerhans cell density in SCCs which developed during etretinate therapy compared with pre-etretinate but the difference was not statistically significant.

CONCLUSIONS

In this study of RTRs, a significant reduction in Langerhans cell densities was observed in SCCs, BCCs and dysplastic lesions compared with normal skin. A reduction in Langerhans cell density in viral warts from RTRs was also observed. A working hypothesis may include a multifactorial etiology for this reduction in Langerhans cell densities. It is possible that human papilloma virus (HPV) infection, by reducing intraepidermal Langerhans cell density, may decrease local immune surveillance and facilitate the development of skin cancers. Ultraviolet radiation and immune suppression may also play a role. The marked depletion of Langerhans cells in skin cancers, precursor lesions and viral warts suggests a central role for Langerhans cells in skin cancer promotion in RTRs.

摘要

背景与设计

朗格汉斯细胞(LC)是表皮中一类独特的抗原呈递细胞,可能在抵御皮肤肿瘤的防御机制中发挥作用。肾移植受者(RTR)发生癌前和恶性皮肤病变的几率显著增加。对局部免疫监视很重要的朗格汉斯细胞,在RTR的皮肤肿瘤中可能会减少或下调,从而促进肿瘤生长。我们调查了15例RTR的29例鳞状细胞癌(SCC)、5例基底细胞癌(BCC)、4例鲍温病、8例发育异常病变(光化性角化病)和3例病毒疣中的朗格汉斯细胞密度,并将其与正常对照皮肤中的朗格汉斯细胞密度进行比较。11例RTR正在接受低剂量依曲替酯作为复发性皮肤癌的化学预防,还评估了低剂量维甲酸治疗对这些患者SCC中朗格汉斯细胞密度的影响。冷冻组织切片中的朗格汉斯细胞用抗人Leu-6单克隆抗体染色。

结果

RTR的正常皮肤与非免疫抑制个体的正常皮肤之间的LC数量无显著差异。与正常皮肤相比,SCC、BCC、发育异常病变和病毒疣的LC/mm²和LC/1000K(角质形成细胞)有统计学显著降低(分别为P < 0.001、P < 0.01、P < 0.001、P < 0.05)。与依曲替酯治疗前相比,依曲替酯治疗期间发生的SCC中朗格汉斯细胞密度有增加趋势,但差异无统计学意义。

结论

在这项对RTR的研究中,与正常皮肤相比,SCC、BCC和发育异常病变中观察到朗格汉斯细胞密度显著降低。在RTR的病毒疣中也观察到朗格汉斯细胞密度降低。一个可行的假设可能包括朗格汉斯细胞密度降低的多因素病因。人乳头瘤病毒(HPV)感染可能通过降低表皮内朗格汉斯细胞密度,减少局部免疫监视并促进皮肤癌发展。紫外线辐射和免疫抑制也可能起作用。皮肤癌、癌前病变和病毒疣中朗格汉斯细胞的明显减少表明朗格汉斯细胞在RTR皮肤癌发生中起核心作用。

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