Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Post-transplantation malignancies: here today, gone tomorrow?

Nature Reviews Clinical Oncology volume 12, pages 705–717 (2015)Cite this article

Subjects

Key Points

  • Cancer risk increases in transplant recipients, accounting for 10–30% of deaths in this patient population; younger recipients have the greatest increase in cancer risk, and the aggressiveness of cancers is also increased in transplant recipients

  • A pro-tumorigenic environment exists in transplant recipients because immunosuppressive drugs that prevent allograft rejection also prevent immune recognition of tumour cells and promote potentially carcinogenic viral infections

  • Reliable and practical strategies that induce donor-specific immunological tolerance to a transplanted organ would likely normalize the incidence of post-transplantation malignancies; however, success with these strategies thus far remains elusive

  • mTOR inhibitors have immunosuppressive and anti-cancer effects that reduce the incidence and prevent recurrence of some post-transplantation tumours, but only partial inhibition occurs and the adverse effects must be counterbalanced

  • Reduced need for immunosuppression, owing to improved development of new (tolerogenic) therapeutic strategies provides the best future hope for combating this increased risk of post-transplantation malignancy

Abstract

From the early days of transplantation onwards, increased cancer development in transplant recipients, who require immunosuppression to avoid graft rejection, has been recognized. Registry data indicate that approximately 10–30% of deaths are attributed to post-transplant malignancy, with an upward trend in this incidence as more patients have been exposed to chronic lifelong immunosuppression. In this Review, the overall incidence and most frequent types of cancer encountered are summarized, along with information about which transplant recipients are at the greatest risk of malignancy. Reasons for why differences exist in susceptibility to cancer in this patient population are examined, and approaches that might improve our understanding of the options available for reducing the incidence of this adverse effect of immunosuppression are described. Whether anti-rejection drugs have been successful in diminishing overall immunosuppressive burden, and consequently show any promise for decreasing post-transplant malignancies is also discussed. The topic shifts to one class of conventional anti-rejection drugs, the mammalian target of rapamycin (mTOR) inhibitors, which paradoxically have both immunosuppressive and anti-neoplastic properties. The complex activities of mTOR are reviewed in order to provide context for how these seemingly opposing effects are possible, and the latest clinical data on use of mTOR inhibitors in the clinic are discussed. The current and future perspectives on how best to normalize these unacceptably high rates of post-transplantation malignancies are highlighted.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Effects of mTOR inhibitors on allograft survival and tumour development.

Similar content being viewed by others

References

  1. Schneck, S. A. & Penn, I. De-novo brain tumours in renal-transplant recipients. Lancet 1, 983–986 (1971).

    Article  CAS  PubMed  Google Scholar 

  2. Penn, I., Hammond, W., Brettschneider, L. & Starzl, T. E. Malignant lymphomas in transplantation patients. Transplant. Proc. 1, 106–112 (1969).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Penn, I. Occurrence of cancers in immunosuppressed organ transplant recipients. Clin. Transplant. 1998, 147–158 (1998).

    Google Scholar 

  4. Chapman, J. R., Webster, A. C. & Wong, G. Cancer in the transplant recipient. Cold Spring Harb. Perspect. Med. 3, 3:a015677 (2013).

    Article  PubMed  Google Scholar 

  5. Chapman, J. R. & Webster, A. C. Cancer after renal transplantation: the next challenge. Am. J. Transplant. 4, 841–842 (2004).

    Article  PubMed  Google Scholar 

  6. Buell, J. F., Gross, T. G. & Woodle, E. S. Malignancy after transplantation. Transplantation 80, S254–S264 (2005).

    Article  PubMed  Google Scholar 

  7. Miao, Y. et al. De novo cancers arising in organ transplant recipients are associated with adverse outcomes compared with the general population. Transplantation 87, 1347–1359 (2009).

    Article  PubMed  Google Scholar 

  8. Webster, A. C., Wong, G. & McDonald, S. Chapter 10: Cancer report. ANZA data registry [online], (2008).

    Google Scholar 

  9. van de Wetering, J., Roodnat, J. I., Haemke, A. C., Hoitsma, A. J. & Weimar, W. Patient survival after the diagnosis of cancer in renal transplant recipients: a nested case-control study. Transplantation 90, 1542–1546 (2010).

    Article  PubMed  Google Scholar 

  10. Penn, I. Occurrence of cancer in immune deficiencies. Cancer 34, 858–866 (1974).

    Article  Google Scholar 

  11. Beyaert, R. et al. Cancer risk in immune-mediated inflammatory diseases (IMID). Mol. Cancer 12, 98–109 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Grulich, A. E., van Leeuwen, M. T., Falster, M. O. & Vajdic, C. M. Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 370, 59–67 (2007).

    Article  PubMed  Google Scholar 

  13. Cobucci, R. N. et al. Assessing the impact of HAART on the incidence of defining and non-defining AIDS cancers among patients with HIV/AIDS: a systematic review. J. Infect. Public Health 8, 1–10 (2015).

    Article  PubMed  Google Scholar 

  14. Lebbé, C., Legendre, C. & Francès, C. Kaposi sarcoma in transplantation. Transplant. Rev. 22, 252–261 (2008).

    Article  Google Scholar 

  15. Madeleine, M. M., Finch, J. L., Lynch, C. F., Goodman, M. T. & Engels, E. A. HPV-related cancers after solid organ transplantation in the United States. Am. J. Transplant. 13, 3202–3209 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hortobagyi, G. N. Treatment of breast cancer. N. Engl. J. Med. 339, 974–984 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. Hall, E. C., Pfeiffer, R. M., Segev, D. L. & Engels, E. A. Cumulative incidence of cancer after solid organ transplantation. Cancer 119, 2300–2308 (2013).

    Article  PubMed  Google Scholar 

  18. Penn, I. Cancers complicating organ transplantation. N. Engl. J. Med. 323, 1767–1769 (1990).

    Article  CAS  PubMed  Google Scholar 

  19. Kleinclauss, F. et al. Prostate cancer in renal transplant recipients. Nephrol. Dial. Transplant. 23, 2374–2380 (2008).

    Article  PubMed  Google Scholar 

  20. Brewer, J. D. et al. Malignant melanoma in solid transplant recipients: collection of database cases and comparison with surveillance, epidemiology, and end results data for outcome analysis. Arch. Dermatol. 147, 790–796 (2011).

    Article  PubMed  Google Scholar 

  21. Wisgerhof, H. C., Wolterbeek, R., de Fijter, J. W., Willemze, R. & Bouwes Bavinck, J. N. Kidney transplant recipients with cutaneous squamous cell carcinoma have an increased risk of internal malignancy. J. Invest. Dermatol. 132, 2176–2183 (2012).

    Article  CAS  PubMed  Google Scholar 

  22. Webster, A. C., Craig, J. C., Simpson, J. M., Jones, M. P. & Chapman, J. R. Identifying high risk groups and quantifying absolute risk of cancer after kidney transplantation: a cohort study of 15183 recipients. Am. J. Transplant. 7, 2140–2151 (2007).

    Article  CAS  PubMed  Google Scholar 

  23. Kiberd, B. A., Keough-Ryan, T. & Clase, C. M. Screening for prostate, breast and colorectal cancer in renal transplant recipients. Am. J. Transplant. 3, 619–625 (2003).

    Article  PubMed  Google Scholar 

  24. Walter, L. C. & Covinsky, K. E. Cancer screening in elderly patients: a framework for individualized decision making. JAMA 285, 2750–2756 (2001).

    Article  CAS  PubMed  Google Scholar 

  25. Stockfleth, E. & Claas, U. (eds) Skin cancer after organ transplantation (Springer, 2009).

    Book  Google Scholar 

  26. Zur Hausen, H. Infections causing human cancer (Wiley-VCH Verlag GmbH & Co. KGaA, 2006).

    Book  Google Scholar 

  27. Euvrard, S., Kanitakis, J. & Claudy, A. Skin cancers after organ transplantation. N. Engl. J. Med. 348, 1681–1691 (2003).

    Article  PubMed  Google Scholar 

  28. Ulrich, C., Kanitakis, J., Stockfleth, E. & Euvrard, S. Skin cancer in organ transplant recipients—where do we stand today? Am. J. Transplant. 8, 2192–2198 (2008).

    Article  CAS  PubMed  Google Scholar 

  29. de Gruijl, F. R. & Voskamp, P. in Skin cancer after organ transplantation (eds Stockfleth, E. & Claas, U.) 101–108 (Springer, 2009).

    Book  Google Scholar 

  30. Bock, A., Bliss, R. L., Matas, A. & Little, J. A. Human leucocyte antigen type as a risk factor for nonmelanomatous skin cancer in patients after renal transplantation. Transplantation 78, 775–778 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Czarnecki, D. et al. Skin cancers and HLA frequencies in renal transplant recipients. Dermatology 185, 9–11 (1992).

    Article  CAS  PubMed  Google Scholar 

  32. Bouwes Bavinck, J. N. et al. Relation between HLA antigens and skin cancer in renal transplant recipients in Queensland, Australia. J. Invest. Dermatol. 108, 708–711 (1997).

    Article  CAS  PubMed  Google Scholar 

  33. Bouwes Bavinck, J. N. et al. On a possible protective effect of HLA A11 against skin cancer and keratotic skin lesions in renal transplant recipients. J. Invest. Dermatol. 97, 269–272 (1991).

    Article  CAS  PubMed  Google Scholar 

  34. Schlienger, J. L., Luca, F., Vinzio, S. & Pradignac, A. Obésité et cancer [French]. Rev. Med. Interne 30, 776–782 (2009).

    Article  PubMed  Google Scholar 

  35. Calle, E. E., Rodriguez, C., Walker-Thurmond, K. & Thun, M. J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U. S. adults. N. Engl. J. Med. 348, 1625–1638 (2003).

    Article  PubMed  Google Scholar 

  36. Agraharkar, M. L., Cinclair, R. D., Kuo, Y. F., Daller, J. A. & Shahinian, V. B. Risk of malignancy with long-term immunosuppression in renal transplant recipients. Kidney Int. 66, 383–389 (2004).

    Article  PubMed  Google Scholar 

  37. Knoll, G. et al. Canadian Society of Transplantation consensus guidelines on eligibility for kidney transplantation. CMAJ 173, 1181–1184 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Batabyal, P., Chapman, J. R., Wong, G., Craig, J. C. & Tong, A. Clinical practice guidelines on wait-listing for kidney transplantation: consistent and equitable? Transplantation 94, 703–713 (2012).

    Article  PubMed  Google Scholar 

  39. Kauffman, H. M., Cherikh, W. S., McBride, M. A., Cheng, Y. & Hanto, D. W. Deceased donors with a past history of malignancy: an organ procurement and transplantation network/united network for organ sharing update. Transplantation 84, 272–274 (2007).

    Article  PubMed  Google Scholar 

  40. Nalesnik, M. A. et al. Donor-transmitted malignancies in organ transplantation: assessment of clinical risk. Am. J. Transplant. 11, 1140–1147 (2011).

    Article  CAS  PubMed  Google Scholar 

  41. US Department of Health & Human Services. Organ Procurement and Transplantation Network: Policies [online], (2015).

  42. Corthay, A. Does the immune system naturally protect against cancer? Front. Immunol. 5, 197–204 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Burnet, F. M. The concept of immunological surveillance. Prog. Exp. Tumour Res. 13, 1–27 (1970).

    Article  CAS  Google Scholar 

  44. Thomas, L. On immunosurveillance in human cancer. Yale J. Biol. Med. 55, 329–333 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Kinlen, L. J. et al. Prospective study of cancer in patients with hypogammaglobulinaemia. Lancet 1, 263–266 (1985).

    Article  CAS  PubMed  Google Scholar 

  46. Mueller, B. U. & Pizzo, P. A. Cancer in children with primary or secondary immunodeficiencies. J. Paediatr. 126, 1–10 (1995).

    Article  CAS  Google Scholar 

  47. Gatti, R. A. & Good, R. A. Occurrence of malignancy in immunodeficiency diseases. A literature review. Cancer 28, 89–98 (1971).

    Article  CAS  PubMed  Google Scholar 

  48. Salavoura, K., Kolialexi, A., Tsangaris, G. & Mavrou, A. Development of cancer in patients with primary immunodeficiencies. Anticancer Res. 28, 1263–1269 (2008).

    PubMed  Google Scholar 

  49. Couzin-Frankel, J. Breakthrough of the year 2013. Cancer immunotherapy. Science 342, 1432–1433 (2013).

    Article  CAS  PubMed  Google Scholar 

  50. Hodi, F. S. et al. Improved survival with ipilimumab in patients with metastatic melanoma. N. Engl. J. Med. 363, 711–723 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Topalian, S. L. et al. Safety, activity, and immune correlates of anti-PD 1 antibody in cancer. N. Engl. J. Med. 366, 2443–2454 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Shankaran, V. et al. IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature 410, 1107–1111 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Girardi, M. et al. Regulation of cutaneous malignancy by γδ T cells. Science 294, 605–609 (2001).

    Article  CAS  PubMed  Google Scholar 

  54. Dunn, G. P., Bruce, A. T., Ikeda, H., Old, L. J. & Schreiber, R. D. Cancer immunoediting: from immunosurveillance to tumour escape. Nat. Immunol. 3, 991–998 (2002).

    Article  CAS  PubMed  Google Scholar 

  55. Gasser, S., Orsulic, S., Brown, E. J. & Raulet, D. H. The DNA damage pathway regulates innate immune system ligands of the NKG2D receptor. Nature 436, 1186–1190 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Bauer, S. et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science 285, 727–729 (1999).

    Article  CAS  PubMed  Google Scholar 

  57. Joseph, C. G. et al. Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science 343, 152–157 (2014).

    Article  CAS  PubMed  Google Scholar 

  58. Hojo, M. et al. Cyclosporine induces cancer progression by a cell-autonomous mechanism. Nature 397, 530–534 (1999).

    Article  CAS  PubMed  Google Scholar 

  59. Kuschal, C. et al. Skin cancer in organ transplant recipients: effects of immunosuppressive medications on DNA repair. Exp. Dermatol. 21, 2–6 (2012).

    Article  CAS  PubMed  Google Scholar 

  60. Thoms, K. M. et al. Cyclosporin A, but not everolimus, inhibits DNA repair mediated by calcineurin: implications for tumorigenesis under immunosuppression. Exp. Dermatol. 20, 232–236 (2011).

    Article  CAS  PubMed  Google Scholar 

  61. Ori, Y. et al. Effect of immunosuppressive drugs on spontaneous DNA repair in human peripheral blood mononuclear cells. Biomed. Pharmacother. 66, 409–413 (2012).

    Article  CAS  PubMed  Google Scholar 

  62. Herman, M. et al. Effect of cyclosporin A on DNA repair and cancer incidence in kidney transplant recipients. J. Lab. Clin. Med. 137, 14–20 (2001).

    Article  CAS  PubMed  Google Scholar 

  63. Weischer, M., Röcken, M. & Berneburg, M. Calcineurin inhibitors and rapamycin: cancer protection or promotion? Exp. Dermatol. 16, 385–393 (2007).

    Article  CAS  PubMed  Google Scholar 

  64. O'Donovan, P. et al. Azathioprine and UVA light generate mutagenic oxidative DNA damage. Science 309, 1871–1874 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Hofbauer, G. F. et al. Reversal of UVA skin photosensitivity and DNA damage in kidney transplant recipients by replacing azathioprine. Am. J. Transplant. 12, 218–225 (2012).

    Article  CAS  PubMed  Google Scholar 

  66. Folkman, J. The role of angiogenesis in tumour growth. Semin. Cancer Biol. 3, 65–71 (1992).

    CAS  PubMed  Google Scholar 

  67. Folkman, J. What is the evidence that tumours are angiogenesis dependent? J. Natl Cancer Inst. 82, 4–6 (1990).

    Article  CAS  PubMed  Google Scholar 

  68. Guba, M. et al. Rapamycin inhibits primary and metastatic tumour growth by antiangiogenesis: involvement of vascular endothelial growth factor. Nat. Med. 8, 128–135 (2002).

    Article  CAS  PubMed  Google Scholar 

  69. Koehl, G. et al. Rapamycin protects allografts from rejection while simultaneously attacking tumours in immunosuppressed mice. Transplantation 77, 1319–1326 (2004).

    Article  CAS  PubMed  Google Scholar 

  70. Basu, A. et al. Overexpression of vascular endothelial growth factor and the development of post-transplantation cancer. Cancer Res. 68, 5689–5698 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Shihab, F. S., Bennett, W. M., Yi, H. & Andoh, T. F. Expression of vascular endothelial growth factor and its receptors Flt 1 and KDR/Flk 1 in chronic cyclosporine nephrotoxicity. Transplantation 72, 164–168 (2001).

    Article  CAS  PubMed  Google Scholar 

  72. Zhou, A. Y. & Ryeom, S. Cyclosporin A promotes tumour angiogenesis in a calcineurin-independent manner by increasing mitochondrial reactive oxygen species. Mol. Cancer Res. 12, 1663–1676 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Hernández, G. L. et al. Selective inhibition of vascular endothelial growth factor-mediated angiogenesis by cyclosporin A: roles of the nuclear factor of activated T cells and cyclooxygenase 2. J. Exp. Med. 193, 607–620 (2001).

    Article  PubMed  PubMed Central  Google Scholar 

  74. Koehl, G. et al. MMF inhibits tumour growth and angiogenesis in vitro, but has variable anti-tumour effects in vivo possibly related to bioavailability. Transplantation 83, 607–614 (2007).

    Article  CAS  PubMed  Google Scholar 

  75. Cherikh, W. S. et al. Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation. Transplantation 76, 1289–1293 (2003).

    Article  CAS  PubMed  Google Scholar 

  76. Paya, C. V. et al. Epstein-Barr virus-induced posttransplant lymphoproliferative disorders. Transplantation 68, 1517–1525 (1999).

    Article  CAS  PubMed  Google Scholar 

  77. Kirk, A. D. et al. Dissociation of depletional induction and posttransplant lymphoproliferative disease in kidney recipients treated with alemtuzumab. Am. J. Transplant. 7, 2619–2625 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Waldmann, H. et al. Elimination of graft-versus-host disease by in-vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (CAMPATH 1). Lancet 2, 483–486 (1984).

    Article  CAS  PubMed  Google Scholar 

  79. Knechtle, S. J. et al. Campath-1H induction plus Rapamycin monotherapy for renal transplantation: results of a pilot study. Am. J. Transplant. 3, 722–730 (2003).

    Article  CAS  PubMed  Google Scholar 

  80. Yao, S., Zhu, Y. & Chen, L. Advances in targeting cell surface signalling molecules for immune modulation. Nat. Rev. Drug Discov. 12, 130–146 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Eggermont, A. M., Spatz, A. & Robert, C. Cutaneous melanoma. Lancet 383, 816–827 (2014).

    Article  CAS  PubMed  Google Scholar 

  82. Nindl, I. & Rosl, F. Molecular concepts of virus infections causing skin cancer in organ transplant recipients. Am. J. Transplant. 8, 2199–2204 (2008).

    Article  CAS  PubMed  Google Scholar 

  83. Meyer, T. et al. Association of human papillomavirus infections with cutaneous tumours in immunosuppressed patients. Transpl. Int. 16, 146–153 (2003).

    Article  PubMed  Google Scholar 

  84. Martinez, O. M. & de Gruijl, F. R. Molecular and immunologic mechanisms of cancer pathogenesis in solid organ transplant recipients. Am. J. Transplant. 8, 2205–2211 (2008).

    Article  CAS  PubMed  Google Scholar 

  85. Shlomai, A., de Jong, Y. P. & Rice, C. M. Virus associated malignancies: the role of viral hepatitis in hepatocellular carcinoma. Semin. Cancer Biol. 26, 78–88 (2014).

    Article  CAS  PubMed  Google Scholar 

  86. Buell, J. F. et al. Immunosuppression and Merkel cell cancer. Transplant. Proc. 34, 1780–1781 (2002).

    Article  CAS  PubMed  Google Scholar 

  87. Spurgeon, M. E. & Lambert, P. F. Merkel cell polyomavirus: a newly discovered human virus with oncogenic potential. Virology 435, 118–130 (2013).

    Article  CAS  PubMed  Google Scholar 

  88. Chang, H. H. & Ganem, D. A unique herpesviral transcriptional programme in KSHV-infected lymphatic endothelial cells leads to mTORC1 activation and rapamycin sensitivity. Cell Host Microbe 13, 429–440 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Nichols, L. A., Adang, L. A. & Kedes, D. H. Rapamycin blocks production of KSHV/HHV8: insights into the anti-tumour activity of an immunosuppressant drug. PLoS ONE 6, e14535 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Soliman, A., Fathy, A., Khashab, S., Shaheen, N. & Soliman, M. Sirolimus conversion may suppress viral replication in hepatitis C virus-positive renal transplant candidates. Exp. Clin. Transplant. 11, 408–411 (2013).

    Article  PubMed  Google Scholar 

  91. Peng, L., Liang, D., Tong, W., Li, J. & Yuan, Z. Hepatitis C virus NS5A activates the mammalian target of rapamycin (mTOR) pathway, contributing to cell survival by disrupting the interaction between FK506-binding protein 38 (FKBP38) and mTOR. J. Biol. Chem. 285, 20870–20881 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Esser-Nobis, K., Harak, C., Schult, P., Kusov, Y. & Lohmann, V. Novel perspectives for hepatitis A virus therapy revealed by comparative analysis of hepatitis C virus and hepatitis A virus RNA replication. Hepatology 62, 397–408 (2015).

    Article  CAS  PubMed  Google Scholar 

  93. Ye, L. et al. Mycophenolate mofetil inhibits hepatitis C virus replication in human hepatic cells. Virus Res. 168, 33–40 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Holmes, M. V. et al. Prospective monitoring of Epstein-Barr virus DNA in adult renal transplant recipients during the early posttransplant period: role of mycophenolate mofetil. Transplantation 87, 852–856 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. Morton, M. et al. Epstein-Barr virus infection in adult renal transplant recipients. Am. J. Transplant. 14, 1619–1629 (2014).

    Article  CAS  PubMed  Google Scholar 

  96. Sampaio, M. S., Cho, Y. W., Shah, T., Bunnapradist, S. & Hutchinson, I. V. Association of immunosuppressive maintenance regimens with posttransplant lymphoproliferative disorder in kidney transplant recipients. Transplantation 93, 73–81 (2012).

    Article  CAS  PubMed  Google Scholar 

  97. Liacini, A., Seamone, M. E., Muruve, D. A. & Tibbles, L. A. Anti-BK virus mechanisms of sirolimus and leflunomide alone and in combination: toward a new therapy for BK virus infection. Transplantation 90, 1450–1457 (2010).

    Article  CAS  PubMed  Google Scholar 

  98. Hirsch, H. H., Lu, M. & Wernli, M. Polyomavirus BK (BKV) replication in renal tubular epithelial cells is inhibited by mTOR inhibitors, but activated by tacrolimus in a pathway involving the FKBP12 [abstract 497]. Am. J. Transplant. 11, S179 (2011).

    Article  Google Scholar 

  99. Acott, P. D., O'Regan, P. A., Lee, S. H. & Crocker, J. F. In vitro effect of cyclosporin A on primary and chronic BK polyoma virus infection in Vero E6 cells. Transpl. Infect. Dis. 10, 385–390 (2008).

    Article  CAS  PubMed  Google Scholar 

  100. Peel, M. & Scribner, A. Cyclophilin inhibitors as antiviral agents. Bioorg. Med. Chem. Lett. 23, 4485–4492 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Opelz, G. & Dohler, B. Lymphomas after solid organ transplantation: a collaborative transplant study report. Am. J. Transplant. 4, 222–230 (2004).

    Article  PubMed  Google Scholar 

  102. Ganschow, R., Schulz, T., Meyer, T., Broering, D. C. & Burdelski, M. Low-dose immunosuppression reduces the incidence of post-transplant lymphoproliferative disease in paediatric liver graft recipients. J. Paediatr. Gastroenterol. Nutr. 38, 198–203 (2004).

    Article  CAS  Google Scholar 

  103. Dharnidharka, V. R. & Stevens, G. Risk for post-transplant lymphoproliferative disorder after polyclonal antibody induction in kidney transplantation. Paediatr. Transplant. 9, 622–626 (2005).

    Article  Google Scholar 

  104. Magliocca, J. F. & Knechtle, S. J. The evolving role of alemtuzumab (Campath-1H) for immunosuppressive therapy in organ transplantation. Transpl. Int. 19, 705–714 (2006).

    Article  CAS  PubMed  Google Scholar 

  105. Hanaway, M. J. et al. Alemtuzumab induction in renal transplantation. N. Engl. J. Med. 364, 1909–1919 (2011).

    Article  CAS  PubMed  Google Scholar 

  106. Vincenti, F. et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am. J. Transplant. 10, 535–546 (2010).

    Article  CAS  PubMed  Google Scholar 

  107. Masson, P., Henderson, L., Chapman, J. R., Craig, J. C. & Webster, A. C. Belatacept for kidney transplant recipients. Cochrane Database Syst. Rev. 11, CD010699 (2014).

    Google Scholar 

  108. Vincenti, F. et al. Randomized phase 2b trial of tofacitinib (CP-690550) in de novo kidney transplant patients: efficacy, renal function and safety at 1 year. Am. J. Transplant. 12, 2446–2456 (2012).

    Article  CAS  PubMed  Google Scholar 

  109. Page, E. K., Dar, W. A. & Knechtle, S. J. Tolerogenic therapies in transplantation. Front. Immunol. 3, 198–211 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Page, A. et al. CD40 blockade combines with CTLA4Ig and sirolimus to produce mixed chimerism in an MHC-defined rhesus macaque transplant model. Am. J. Transplant. 12, 115–125 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Leventhal, J. et al. Chimerism and tolerance without GVHD or engraftment syndrome in HLA-mismatched combined kidney and haematopoietic stem cell transplantation. Sci. Transl. Med. 4, 124ra28 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Kawai, T. et al. HLA-mismatched renal transplantation without maintenance immunosuppression. N. Engl. J. Med. 358, 353–361 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Geissler, E. K. The ONE study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplantation Res. 1, 11 (2012).

    Article  Google Scholar 

  114. Wood, K. J., Bushell, A. & Hester, J. Regulatory immune cells in transplantation. Nat. Rev. Immunol. 12, 417–430 (2012).

    Article  CAS  PubMed  Google Scholar 

  115. Dantal, J. et al. Effect of long-term immunosuppression in kidney-graft recipients on cancer incidence: randomised comparison of two cyclosporin regimens. Lancet 351, 623–628 (1998).

    Article  CAS  PubMed  Google Scholar 

  116. Vivarelli, M. et al. Analysis of risk factors for tumour recurrence after liver transplantation for hepatocellular carcinoma: Key role of immunosuppression. Liver Transpl. 11, 497–503 (2005).

    Article  PubMed  Google Scholar 

  117. Kawai, T. et al. Long-term results in recipients of combined HLA-mismatched kidney and bone marrow transplantation without maintenance immunosuppression. Am. J. Transplant. 14, 1599–1611 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Scandling, J. D. et al. Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and haematopoietic cell transplantation. Am. J. Transplant. 15, 695–704 (2015).

    Article  CAS  PubMed  Google Scholar 

  119. Flechner, S. et al. De novo immunosuppression with mammalian target of rapamycin inhibitors and posttransplantation malignancy in focus. Transplant. Proc. 41, S42–S44 (2009).

    Article  CAS  PubMed  Google Scholar 

  120. Geissler, E. K., Schlitt, H. J. & Thomas, G. mTOR, cancer and transplantation. Am. J. Transplant. 8, 2212–2218 (2008).

    Article  CAS  PubMed  Google Scholar 

  121. Guba, M., Graeb, C., Jauch, K. W. & Geissler, E. K. Pro and anti-cancer effects of immunosuppressive agents used in organ transplantation. Transplantation 77, 1777–1782 (2004).

    Article  CAS  PubMed  Google Scholar 

  122. Dennis, P. B. et al. Mammalian TOR: a homeostatic ATP sensor. Science 294, 1102–1105 (2001).

    Article  CAS  PubMed  Google Scholar 

  123. Albert, V. & Hall, M. N. mTOR signalling in cellular and organismal energetics. Curr. Opin. Cell Biol. 33, 55–66 (2014).

    Article  CAS  PubMed  Google Scholar 

  124. Wullschleger, S., Loewith, R. & Hall, M. N. TOR signalling in growth and metabolism. Cell 124, 471–484 (2006).

    Article  CAS  PubMed  Google Scholar 

  125. Huang, S. & Houghton, P. J. Targeting mTOR signalling for cancer therapy. Curr. Opin. Pharmacol. 3, 371–377 (2003).

    Article  CAS  PubMed  Google Scholar 

  126. Jacinto, E. & Hall, M. N. Tor signalling in bugs, brain and brawn. Nat. Rev. Mol. Cell Biol. 4, 117–126 (2003).

    Article  CAS  PubMed  Google Scholar 

  127. Zarogoulidis, P. et al. mTOR pathway: A current, up-to-date mini-review (Review). Oncol. Lett. 8, 2367–2370 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Tee, A. R. Fundamental for life: mTOR orchestrates developing biological systems. Semin. Cell Dev. Biol. 36, 66–67 (2014).

    Article  CAS  PubMed  Google Scholar 

  129. Shimobayashi, M. & Hall, M. N. Making new contacts: the mTOR network in metabolism and signalling crosstalk. Nat. Rev. Mol. Cell Biol. 15, 155–162 (2014).

    Article  CAS  PubMed  Google Scholar 

  130. Wells, A. D. et al. Requirement for T cell apoptosis in the induction of peripheral transplantation tolerance. Nat. Med. 5, 1303–1307 (1999).

    Article  CAS  PubMed  Google Scholar 

  131. Li, Y., Zheng, X. X., Li, X. C., Zand, M. S. & Strom, T. B. Combined co-stimulation blockade plus rapamycin but not cyclosporine produces permanent engraftment. Transplantation 66, 1387–1388 (1998).

    Article  CAS  PubMed  Google Scholar 

  132. Li, Y. et al. Blocking both signal 1 and signal 2 of T cell activation prevents apoptosis of alloreactive T cells and induction of peripheral allograft tolerance. Nat. Med. 5, 1298–1302 (1999).

    Article  CAS  PubMed  Google Scholar 

  133. Battaglia, M., Stabilini, A. & Roncarolo, M. G. Rapamycin selectively expands CD4+CD25+FoxP3+ regulatory T cells. Blood 105, 4743–4748 (2005).

    Article  CAS  PubMed  Google Scholar 

  134. Zeiser, R. et al. Differential impact of mammalian target of rapamycin inhibition on CD4+CD25+Foxp3+ regulatory T cells compared with conventional CD4+ T cells. Blood 111, 453–462 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Hendrikx, T. K. et al. Monotherapy rapamycin allows an increase of CD4+ CD25bright+ FoxP3+ T cells in renal recipients. Transpl. Int. 22, 884–891 (2009).

    Article  CAS  PubMed  Google Scholar 

  136. Taner, T., Hackstein, H., Wang, Z., Morelli, A. E. & Thomson, A. W. Rapamycin-treated, alloantigen-pulsed host dendritic cells induce Ag-specific T cell regulation and prolong graft survival. Am. J. Transplant. 5, 228–236 (2005).

    Article  CAS  PubMed  Google Scholar 

  137. Haidinger, M. et al. A versatile role of mammalian target of Rapamycin in human dendritic cell function and differentiation. J. Immunol. 185, 3919–3931 (2010).

    Article  CAS  PubMed  Google Scholar 

  138. Thomson, A. W., Turnquist, H. R. & Raimondi, G. Immunoregulation functions of mTOR inhibition. Nat. Rev. Immunol. 9, 324–337 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Pollizzi, K. N. & Powell, J. D. Regulation of T cells by mTOR: the known knowns and the known unknowns. Trends Immunol. 36, 13–20 (2015).

    Article  CAS  PubMed  Google Scholar 

  140. Delgoffe, G. M. et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signalling by mTORC1 and mTORC2. Nat. Immunol. 12, 295–303 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Turner, A. P. et al. Sirolimus enhances the magnitude and quality of viral-specific CD8+ T cell responses to vaccinia virus vaccination in rhesus macaques. Am. J. Transplant. 11, 613–618 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Araki, K. et al. mTOR regulates memory CD8 T cell differentiation. Nature 460, 108–112 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Rao, R. R., Li, Q., Odunsi, K. & Shrikant, P. A. The mTOR kinase determines effector versus memory CD8+ T cell fate by regulating the expression of transcription factors T bet and Eomesodermin. Immunity 32, 67–78 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Amiel, E. et al. Inhibition of mechanistic target of rapamycin promotes dendritic cell activation and enhances therapeutic autologous vaccination in mice. J. Immunol. 189, 2151–2158 (2012).

    Article  CAS  PubMed  Google Scholar 

  145. Rovira, J. et al. A colour-coded reporter model to study the effect of immunosuppressants on CD8+ T cell memory in antitumour and alloimmune responses. Transplantation 95, 54–62 (2013).

    Article  CAS  PubMed  Google Scholar 

  146. Li, Q. et al. A central role for mTOR kinase in homeostatic proliferation induced CD8+ T cell memory and tumour immunity. Immunity 34, 541–553 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Majewski, M. et al. Immunosuppressive TOR kinase inhibitor everolimus (RAD) suppresses growth of cells derived from posttransplant lymphoproliferative disorder at allograft-protecting doses. Transplantation 75, 1710–1717 (2003).

    Article  CAS  PubMed  Google Scholar 

  148. Majewski, M. et al. The immunosuppressive macrolide RAD inhibits growth of human Epstein-Barr virus-transformed B lymphocytes in vitro and in vivo: A potential approach to prevention and treatment of posttransplant lymphoproliferative disorders. Proc. Natl Acad. Sci. USA 97, 4285–4290 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Spangle, J. M. & Münger, K. The human papillomavirus type 16 E6 oncoprotein activates mTORC1 signalling and increases protein synthesis. J. Virol. 84, 9398–9407 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Ashrafi, F., Shahidi, S., Ebrahimi, Z. & Mortazavi, M. Outcome of rapamycin therapy for post-transplant-lymphoproliferative disorder after kidney transplantation: case series. Int. J. Haematol. Oncol. Stem Cell Res. 9, 26–32 (2015).

    Google Scholar 

  151. Petroulakis, E., Mamane, Y., Le Bacquer, O., Shahbazian, D. & Sonenberg, N. mTOR signalling: implications for cancer and anticancer therapy. Br. J. Cancer 94, 195–199 (2006).

    Article  CAS  PubMed  Google Scholar 

  152. Guertin, D. A. & Sabatini, D. M. Defining the role of mTOR in cancer. Cancer Cell 12, 9–22 (2007).

    Article  CAS  PubMed  Google Scholar 

  153. Bjornsti, M. A. & Houghton, P. J. The tor pathway: a target for cancer therapy. Nat. Rev. Cancer 4, 335–348 (2004).

    Article  CAS  PubMed  Google Scholar 

  154. Phung, T. L. et al. Pathological angiogenesis is induced by sustained Akt signalling and inhibited by rapamycin. Cancer Cell 10, 159–170 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Campistol, J. M., Gutierrez-Dalmau, A. & Torregrosa, J. V. Conversion to sirolimus: a successful treatment for posttransplantation Kaposi's sarcoma. Transplantation 77, 760–762 (2004).

    Article  PubMed  Google Scholar 

  156. Stallone, G. et al. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N. Engl. J. Med. 352, 1317–1323 (2005).

    Article  CAS  PubMed  Google Scholar 

  157. Huber, S. et al. Inhibition of the mammalian target of rapamycin impedes lymphangiogenesis. Kidney Int. 71, 771–777 (2007).

    Article  CAS  PubMed  Google Scholar 

  158. Campistol, J. M. Minimizing the risk of posttransplant malignancy. Transplantation 87, S19–S22 (2009).

    Article  PubMed  Google Scholar 

  159. Valantine, H. Is there a role for proliferation signal/mTOR inhibitors in the prevention and treatment of de novo malignancies after heart transplantation? Lessons learned from renal transplantation and oncology. J. Heart Lung Transplant. 26, 557–564 (2007).

    Article  PubMed  Google Scholar 

  160. Webster, A. C., Lee, V. W., Chapman, J. R. & Craig, J. C. Target of rapamycin inhibitors (sirolimus and everolimus) for primary immunosuppression of kidney transplant recipients: a systematic review and meta-analysis of randomized trials. Transplantation 81, 1234–1248 (2006).

    Article  CAS  PubMed  Google Scholar 

  161. Ekberg, H. et al. Reduced exposure to calcineurin inhibitors in renal transplantation. N. Engl. J. Med. 357, 2562–2575 (2007).

    Article  CAS  PubMed  Google Scholar 

  162. Schnitzbauer, A. A., Schlitt, H. J. & Geissler, E. K. Influence of immunosuppressive drugs on the recurrence of hepatocellular carcinoma after liver transplantation: a gap between basic science and clinical evidence. Transplantation 91, 1173–1176 (2011).

    Article  CAS  PubMed  Google Scholar 

  163. Hoogendijk-van den Akker J. M. et al. Two-year randomized controlled prospective trial converting treatment of stable renal transplant recipients with cutaneous invasive squamous cell carcinomas to sirolimus. J. Clin. Oncol. 31, 1317–1323 (2013).

    Article  CAS  PubMed  Google Scholar 

  164. Euvrard, S. et al. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N. Engl. J. Med. 367, 329–339 (2012).

    Article  CAS  PubMed  Google Scholar 

  165. Campbell, S. B., Walker, R., Tai, S. S., Jiang, Q. & Russ, G. R. Randomized controlled trial of sirolimus for renal transplant recipients at high risk for nonmelanoma skin cancer. Am. J. Transplant. 12, 1146–1156 (2012).

    Article  CAS  PubMed  Google Scholar 

  166. Detroyer, D. et al. Resolution of diffuse skin and systemic Kaposi's sarcoma in a renal transplant recipient after introduction of everolimus: a case report. Transpl. Infect. Dis. 17, 303–307 (2015).

    Article  CAS  PubMed  Google Scholar 

  167. Kuang, E., Fu, B., Liang, Q., Myoung, J. & Zhu, F. Phosphorylation of eukaryotic translation initiation factor 4B (EIF4B) by open reading frame 45/p90 ribosomal S6 kinase (ORF45/RSK) signalling axis facilitates protein translation during Kaposi sarcoma-associated herpesvirus (KSHV) lytic replication. J. Biol. Chem. 286, 41171–41182 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  168. Mourah, S. et al. Paradoxical simultaneous regression and progression of lesions in a phase ii study of everolimus in classic kaposi's sarcoma. Br. J. Dermatol. http://dx.doi.org/10.1111/bjd.13897 (2015).

  169. Menon, K. V., Hakeem, A. R. & Heaton, N. D. Meta-analysis: recurrence and survival following the use of sirolimus in liver transplantation for hepatocellular carcinoma. Aliment. Pharmacol. Ther. 37, 411–419 (2013).

    Article  CAS  PubMed  Google Scholar 

  170. Liang, W. et al. Sirolimus-based immunosuppression in liver transplantation for hepatocellular carcinoma: a meta-analysis. Liver Transpl. 18, 62–69 (2012).

    Article  PubMed  Google Scholar 

  171. Chinnakotla, S. et al. Impact of sirolimus on the recurrence of hepatocellular carcinoma after liver transplantation. Liver Transpl. 15, 1834–1842 (2009).

    Article  PubMed  Google Scholar 

  172. Toso, C., Merani, S., Bigam, D. L., Shapiro, A. M. & Kneteman, N. M. Sirolimus-based immunosuppression is associated with increased survival after liver transplantation for hepatocellular carcinoma. Hepatology 51, 1237–1243 (2010).

    Article  CAS  PubMed  Google Scholar 

  173. Zimmerman, M. A. et al. Sirolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma. Liver Transpl. 14, 633–638 (2008).

    Article  PubMed  Google Scholar 

  174. Kneteman, N. M. et al. Sirolimus-based immunosuppression for liver transplantation in the presence of extended criteria for hepatocellular carcinoma. Liver Transpl. 10, 1301–1311 (2004).

    Article  PubMed  Google Scholar 

  175. Schnitzbauer, A. A. et al. A prospective randomised, open-labelled, trial comparing sirolimus-containing versus mTOR-inhibitor-free immunosuppression in patients undergoing liver transplantation for hepatocellular carcinoma. BMC Cancer 10, 190 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  176. Geissler, E. K. et al. Sirolimus use in liver transplant recipients with hepatocellular carcinoma: a randomised, multi-centre, open-label phase 3 trial. Transplantation (in press).

  177. Zhu, A. X. et al. Effect of everolimus on survival in advanced hepatocellular carcinoma after failure of sorafenib: the EVOLVE 1 randomized clinical trial. JAMA 312, 57–67 (2014).

    Article  CAS  PubMed  Google Scholar 

  178. Knoll, G. A. et al. Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data. BMJ 349, g6679 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  179. Yanik, E. L. et al. Sirolimus use and cancer incidence among US kidney transplant recipients. Am. J. Transplant. 15, 129–136 (2015).

    Article  CAS  PubMed  Google Scholar 

  180. Webster, A. C., Wong, G., Craig, J. C. & Chapman, J. R. Managing cancer risk and decision making after kidney transplantation. Am. J. Transplant. 8, 2185–2191 (2008).

    Article  CAS  PubMed  Google Scholar 

  181. Breyer, B. N., Whitson, J. M., Freise, C. E. & Meng, M. V. Prostate cancer screening and treatment in the transplant population: current status and recommendations. J. Urol. 181, 2018–2025 (2009).

    Article  PubMed  Google Scholar 

  182. Wong, G., Chapman, J. R. & Craig, J. C. Cancer screening in renal transplant recipients: what is the evidence? Clin. J. Am. Soc. Nephrol. 3 (Suppl. 2), S87–S100 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  183. Kohli, A., Shaffer, A., Sherman, A. & Kottilil, S. Treatment of hepatitis C: a systematic review. JAMA 312, 631–640 (2014).

    Article  CAS  PubMed  Google Scholar 

  184. Lens, S., Marino, Z. & Forns, X. Efficacy of new direct acting antivirals in transplant recipients and patients with advanced disease. Dig. Liver Dis. 46, S197–S205 (2014).

    Article  CAS  PubMed  Google Scholar 

  185. Vinzón, S. E. et al. Protective vaccination against papillomavirus-induced skin tumours under immunocompetent and immunosuppressive conditions: a preclinical study using a natural outbred animal model. PLoS Pathog. 10, e1003924 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  186. US Renal Data System. USRDS 2012 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States [online], (2012).

  187. Australia and New Zealand Dialysis and Transplant Registry. ANZDATA Registry Report 2010 [online], (2010).

  188. Haynes, R. et al. Alemtuzumab-based induction treatment versus basiliximab-based induction treatment in kidney transplantation (the 3C Study): a randomised trial. Lancet 384, 1684–1690 (2014).

    Article  CAS  PubMed  Google Scholar 

  189. Durrbach, A. et al. A phase III study of belatacept versus cyclosporine in kidney transplants from extended criteria donors (BENEFIT-EXT study). Am. J. Transplant. 10, 547–557 (2010).

    Article  CAS  PubMed  Google Scholar 

  190. Hudes, G. et al. Temsirolimus, interferon α, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 356, 2271–2281 (2007).

    Article  CAS  PubMed  Google Scholar 

  191. Motzer, R. J. et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 372, 449–456 (2008).

    Article  CAS  PubMed  Google Scholar 

  192. Zhang, L. et al. Mammalian target of rapamycin complex 1 orchestrates invariant NKT cell differentiation and effector function. J. Immunol. 193, 1759–1765 (2014).

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Section of Experimental Surgery, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93053, Germany

    Edward K. Geissler

Authors
  1. Edward K. Geissler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edward K. Geissler.

Ethics declarations

Competing interests

E.K.G. has previously received research funding and speaking honoraria from Pfizer Inc.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Geissler, E. Post-transplantation malignancies: here today, gone tomorrow?. Nat Rev Clin Oncol 12, 705–717 (2015). https://doi.org/10.1038/nrclinonc.2015.186

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2015.186

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing