The janus face of immunosuppression – de novo malignancy after renal transplantation: the experience of the Transplantation Center Munich

Abstract

After decades of successful organ transplantation clinicians continue to be troubled by the increasing incidence of cancers under maintenance immunosuppression. In this study, we examined rates of malignancies in 2419 renal transplant recipients transplanted in our institution between 1978 and 2005. In renal transplant recipients the cumulative incidence of cancer after 25 years was 49.3% for all tumors and 39.7% excluding non-melanoma skin cancers, compared with 21% for a normal sex- and age-matched population. The most frequent tumors observed were non-melanoma skin cancers (20.5%), kidney cancers (12.0%), and cancers of the pharynx, larynx, or oral cavity (8.2%). The general increase of cancer risk was 4.3-fold. Independent risk factors for the development of a tumor were male gender, older recipient age, the presence of preformed antibodies before transplantation, and the time on immunosuppression. Interestingly, the use of IL-2-receptor antagonists significantly reduced the tumor risk of transplant recipients. The tumor risk between immunosuppressive drugs typically used for maintenance immunosuppression was not significantly different. However, mammalian target of rapamycin (mTOR) inhibitor-based immunosuppressive protocols showed a clear tendency for lower malignancy rates. De novo malignancies following renal transplantation represent a serious problem endangering the prognosis of otherwise successfully transplanted patients. Future studies will have to address whether optimized immunosuppressive regimens including mTOR-inhibitors are capable of reducing the incidence or preventing the development of posttransplant malignancies.

Calcineurin Inhibitors Modulate CXCR3 Splice Variant Expression and Mediate Renal Cancer Progression

“…[33][34][35][36]43,44 In this study, we showed that CXCR3 and its ligands are overexpressed in human renal cancer, one of the major cancers after solid organ transplantation. 18,45 The two splice variants of CXCR3 mediate distinctly different signals and have completely opposite functions in tumor cells as well as in a variety of normal cell types, such as lymphocytes, endothelial cells, and airway epithelial cells 28,37,39,40 ; CXCR3-A promotes chemotaxis and cell proliferation, whereas CXCR3-B mediates growth inhibition. 28,37,40 Thus, it is likely that signaling through CXCR3-B in renal cancer cells may inhibit cell growth.…”

Clinically Relevant Immunosuppressants Influence UVB-Induced Tumor Size Through Effects on Inflammation and Angiogenesis

“…drugs are responsible for the increased skin cancer risk (16) or to determine the general mechanisms underlying the increased risk (16,60,61). Most transplant recipients are adults when they receive their new organs, and have accumulated years of sunlight-related skin damage.…”

EBV-positive post-transplant lymphoproliferative disorder presenting as primary diffuse large B-cell lymphoma of the central nervous system

“…case, the patient received a long-term immunosuppressive regimen including mycophenolate and tacrolimus, both of which are associated with a higher risk of developing PTLD [15]. EBV infection is a key contributor to the development of PTLD.…”