Infante B, Stallone G, Schena A, Maiorano A, Gesualdo L, Schena F P, Grandaliano G
Dipartimento di Scienze Biomediche-S.C. di Nefrologia, Dialisi e Trapianto, Università degli Studi di Foggia.
G Ital Nefrol. 2006 Jul-Aug;23(4):389-95.
The increased efficiency of immunosuppressive drugs obtained in the last few years has significantly reduced the incidence of acute rejection, prolonging transplant survival rates. The inevitable trade-off was however an increased rate of post-transplant infections and malignancies. Furthermore, this problem might get more and more serious in the next future due to the increasing incidence of cancer in immunosuppressed transplant recipients; the introduction of new immunosuppressive strategies is expected to extend significantly allograft survival. The inclusion of older recipients in transplant programs will also likely increase this problem. Thus, cancer may represent a serious cause of morbidity and mortality in patients otherwise successfully treated by organ transplantation. Nevertheless, effective approaches to deal with malignancies in immunosuppressed patients are still far from the clinical arena. Therefore, once cancer occurs in a transplant recipient, clinicians only have two options: to reduce or withdraw the immunosuppression eventually causing acute or chronic allograft rejection, or to continue the standard immunosuppressive therapy while beginning specific therapy for the malignancy. Several clinical studies suggest that the use of immunosuppressive drugs may result in increased cancer incidence, in transplant as well as autoimmune disease patients. This clinical observation is supported by experimental data showing that these drugs enhance cancer cell growth characteristics and inhibit DNA repair mechanisms, clearly suggesting that the increased incidence of neoplastic disease in patients treated with several immunosuppressive drugs is at least partially independent of their immunosuppressive action. In this scenario it is of particular interest the fact that some immunosuppressive drugs have both an anti-rejection and anti-neoplastic activity. In this review we focus our attention on this potential dual role of immunosuppressive therapy in the development of neoplasia in transplanted patients.
过去几年中免疫抑制药物效率的提高显著降低了急性排斥反应的发生率，延长了移植存活率。然而，不可避免的权衡是移植后感染和恶性肿瘤的发生率增加。此外，由于免疫抑制的移植受者中癌症发病率不断上升，这个问题在未来可能会越来越严重；预计新免疫抑制策略的引入将显著延长同种异体移植物的存活时间。将老年受者纳入移植项目也可能会增加这个问题。因此，癌症可能是器官移植成功治疗的患者发病和死亡的严重原因。然而，处理免疫抑制患者恶性肿瘤的有效方法仍远未应用于临床。因此，一旦移植受者发生癌症，临床医生只有两种选择：减少或停用最终导致急性或慢性同种异体移植排斥反应的免疫抑制，或者在开始针对恶性肿瘤的特异性治疗时继续标准免疫抑制治疗。几项临床研究表明，免疫抑制药物的使用可能会导致移植患者以及自身免疫性疾病患者癌症发病率增加。这一临床观察得到了实验数据的支持，这些数据表明这些药物增强了癌细胞的生长特性并抑制了DNA修复机制，清楚地表明用几种免疫抑制药物治疗的患者肿瘤性疾病发病率的增加至少部分与其免疫抑制作用无关。在这种情况下，一些免疫抑制药物具有抗排斥和抗肿瘤活性这一事实特别令人关注。在这篇综述中，我们将注意力集中在免疫抑制治疗在移植患者肿瘤形成中的这种潜在双重作用上。
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