Stockfleth E, Ulrich C, Meyer T, Christophers E
Department of Dermatology, Christian Albrechts University, Kiel, Germany.
Recent Results Cancer Res. 2002;160:251-8. doi: 10.1007/978-3-642-59410-6_30.
Transplantation of solid organs has been well established as a mode of therapy for the treatment of various end-stage organ diseases for many years. Up to now, it has benefited more than 1 million patients worldwide. The long-term success of organ transplantation depends particularly on the prevention of allograft rejection. Various regimens have been used to suppress hosts' cellular immune responsiveness to the grafted organs. Nowadays immunosuppressive therapies consist mainly in prednisolone, azathioprine, cyclosporine, anti-T-lymphocyte-globulin (ATG), anti-CD 3 antibody (OKT3) and substances of a new generation, such as tacrolimus or mycophenolic acid. However, not only the patient's reactivity to the graft is impaired, but also that to infectious organisms. Chronically altered immune responsiveness is especially associated with a dramatically increased risk of malignancy, most frequently non-Hodgkin's lymphoma and skin cancer. Within the first 5 years of immunosuppression 40% of transplant recipients experience premalignant skin tumors such as actinic keratoses and Bowen's disease, and also such skin cancers as squamous cell carcinomas and basal cell carcinomas. Quite often these have an aggressive biology and an uncommon morphology. Cancer is now responsible for a mortality rate of 5-8% in organ transplant patients. Various risk factors, such as exposure to sun and infections with oncogenic viruses (e.g. HPV) contribute to the already increased risk of dysplasia when lifelong immunosuppression is required. Prophylactic strategies therefore include the development of virus-like particles (VLPs) as anticancer vaccines, which might become a very interesting approach to preventing HPV-associated cancer. The prevention of precancerous conditions and mature skin cancers in grafted patients includes protective clothing and adequate protection of UV-exposed skin regions, including lips, from sunlight with appropriate sunscreen. Close dermatological surveillance through a specialized outpatient department should be ensured to detect potentially fatal skin malignancies at an early stage. Early treatment of precancerous lesions includes topical retinoids, such as tretionin, tazarotene or adapalene. A 5% fluorouracil cream is widely used but shows variable effects on manifest actinic keratoses. As cellular immunity seems to play the major part in the prevention and cure of malignant and premalignant cutaneous neoplasias as well as viral infections, a specific enhancement of the local immunity would be desirable. Imiquimod is one of a class of agents known as immune response modifiers. The drug has been shown to have both antiviral and antitumor activity. Application of immune response activators or modifiers such as imiquimod might be premising in the case of transplant recipients.
多年来，实体器官移植已被公认为是治疗各种终末期器官疾病的一种治疗方式。到目前为止，它已使全球100多万患者受益。器官移植的长期成功尤其取决于预防同种异体移植排斥反应。人们采用了各种方案来抑制宿主对移植器官的细胞免疫反应。如今，免疫抑制疗法主要包括泼尼松龙、硫唑嘌呤、环孢素、抗T淋巴细胞球蛋白（ATG）、抗CD3抗体（OKT3）以及新一代药物，如他克莫司或霉酚酸。然而，不仅患者对移植物的反应性受到损害，而且对感染性生物体的反应性也受到损害。长期改变的免疫反应性尤其与恶性肿瘤风险的显著增加有关，最常见的是非霍奇金淋巴瘤和皮肤癌。在免疫抑制的头5年内，40%的移植受者会出现癌前皮肤肿瘤，如光化性角化病和鲍恩病，以及鳞状细胞癌和基底细胞癌等皮肤癌。这些肿瘤往往具有侵袭性生物学行为和不常见的形态。癌症现在导致器官移植患者的死亡率为5%至8%。各种风险因素，如日晒和致癌病毒（如人乳头瘤病毒）感染，在需要终身免疫抑制的情况下，会使发育异常的风险本已增加。因此，预防策略包括开发病毒样颗粒（VLP）作为抗癌疫苗，这可能成为预防人乳头瘤病毒相关癌症的一种非常有趣的方法。预防移植患者的癌前病变和成熟皮肤癌包括穿防护服，并用适当的防晒霜充分保护暴露于紫外线的皮肤区域，包括嘴唇，使其免受阳光照射。应确保通过专门的门诊部进行密切的皮肤科监测，以便在早期发现潜在致命的皮肤恶性肿瘤。癌前病变的早期治疗包括局部使用维甲酸，如维甲酸、他扎罗汀或阿达帕林。5%的氟尿嘧啶乳膏被广泛使用，但对明显的光化性角化病效果不一。由于细胞免疫似乎在恶性和癌前皮肤肿瘤以及病毒感染的预防和治疗中起主要作用，因此需要特异性增强局部免疫力。咪喹莫特是一类被称为免疫反应调节剂的药物之一。该药物已被证明具有抗病毒和抗肿瘤活性。在移植受者的情况下，应用免疫反应激活剂或调节剂，如咪喹莫特，可能是有前景的。
