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Application of Immune Checkpoint Inhibitors in Solid Organ Transplantation Recipients: A Systematic Review

  • Original research article
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Abstract

Background

Solid organ transplantation (SOT) is a treatment method for end-stage organ diseases and improve their life quality, while using long-term immunosuppressant drugs (ISD) is needed to suppress the function of the immune system. Immune checkpoint inhibitors (ICIs) are a class of anti-tumor drugs that kill tumors by activating the autoimmune system. The primary objective of our systematic review is to investigate the risk factors for organ rejection and the efficacy of ICIs in solid organ transplantation recipients (SOTRs).

Methods

We searched four databases to find relevant articles up to January 2021. A total of 61 articles involving 106 SOTRs met the screening criteria and were included in our systematic review. The collected data were statistical described, and the risk factors were analyzed by logistic regression.

Results

Forty-four patients (41.5%) developed host-versus-graft response (HVGR) after ICIs. mTOR inhibitors (pre-ICIs) (p = 0.069, OR = 0.377, 95% CI 0.132–1.078) and calcineurin inhibitors (post-ICIs) (p = 0.056, OR = 0.375, 95%CI 0.137–1.025) may help reduce the incidence of HVGR. Hormones (pre-ICIs) (p = 0.026, OR = 3.150, 95%CI 1.150–8.628) and anti-metabolites (pre-ICIs) (p = 0.022, OR = 3.214, 95%CI 1.185–8.720) may adversely affect the efficacy of ICIs. Only 35.6% of patients both responded well to ICIs treatment and did not develop HVGR.

Conclusions

Our systematic review summarizes the use of ICIs in SOTRs and evaluates the efficacy of ICIs and the risk factors that induce HVGR. Through risk factor analysis, we found that mTOR inhibitors and calcineurin inhibitors may help to reduce the occurrence of HVGR; hormones and anti-metabolic drugs may have adverse effects on the efficacy of ICIs. In addition, there is a contradictory relationship between the occurrence of HVGR and the efficacy of ICIs.

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Data Availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

References

  1. McDonald-Hyman C, Turka LA, Blazar BR (2015) Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation. Sci Transl Med 7(280):280rv282. https://doi.org/10.1126/scitranslmed.aaa6853

    Article  CAS  Google Scholar 

  2. Neuberger JM, Bechstein WO, Kuypers DR, Burra P, Citterio F, De Geest S, Duvoux C, Jardine AG, Kamar N, Krämer BK, Metselaar HJ, Nevens F, Pirenne J, Rodríguez-Perálvarez ML, Samuel D, Schneeberger S, Serón D, Trunečka P, Tisone G, van Gelder T (2017) Practical recommendations for long-term management of modifiable risks in kidney and liver transplant recipients: a guidance report and clinical checklist by the consensus on managing modifiable risk in transplantation (COMMIT) group. Transplantation 101(4S Suppl2):S1-s56. https://doi.org/10.1097/tp.0000000000001651

    Article  PubMed  Google Scholar 

  3. Meyer KC (2018) Recent advances in lung transplantation. F1000Research. https://doi.org/10.12688/f1000research.15393.1

    Article  PubMed  PubMed Central  Google Scholar 

  4. Cozzi E, Colpo A, De Silvestro G (2017) The mechanisms of rejection in solid organ transplantation. Transfus Apher Sci Off J World Apher Assoc Off J Eur Soc Haemapheresis 56(4):498–505. https://doi.org/10.1016/j.transci.2017.07.005

    Article  Google Scholar 

  5. Koo J, Wang HL (2018) Acute, chronic, and humoral rejection: pathologic features under current immunosuppressive regimes. Surg Pathol Clin 11(2):431–452. https://doi.org/10.1016/j.path.2018.02.011

    Article  PubMed  Google Scholar 

  6. Grulich AE, van Leeuwen MT, Falster MO, Vajdic CM (2007) Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet (London, England) 370(9581):59–67. https://doi.org/10.1016/s0140-6736(07)61050-2

    Article  Google Scholar 

  7. Kalbasi A, Ribas A (2020) Tumour-intrinsic resistance to immune checkpoint blockade. Nat Rev Immunol 20(1):25–39. https://doi.org/10.1038/s41577-019-0218-4

    Article  CAS  PubMed  Google Scholar 

  8. Li B, Chan HL, Chen P (2019) Immune checkpoint inhibitors: basics and challenges. Curr Med Chem 26(17):3009–3025. https://doi.org/10.2174/0929867324666170804143706

    Article  CAS  PubMed  Google Scholar 

  9. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363(8):711–723. https://doi.org/10.1056/NEJMoa1003466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Herbst RS, Baas P, Kim DW, Felip E, Pérez-Gracia JL, Han JY, Molina J, Kim JH, Arvis CD, Ahn MJ, Majem M, Fidler MJ, de Jr Castro G, Garrido M, Lubiniecki GM, Shentu Y, Im E, Dolled-Filhart M, Garon EB (2016) Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet (London, England) 387(10027):1540–1550. https://doi.org/10.1016/s0140-6736(15)01281-7

    Article  CAS  Google Scholar 

  11. Rosenberg JE, Hoffman-Censits J, Powles T, van der Heijden MS, Balar AV, Necchi A, Dawson N, O’Donnell PH, Balmanoukian A, Loriot Y, Srinivas S, Retz MM, Grivas P, Joseph RW, Galsky MD, Fleming MT, Petrylak DP, Perez-Gracia JL, Burris HA, Castellano D, Canil C, Bellmunt J, Bajorin D, Nickles D, Bourgon R, Frampton GM, Cui N, Mariathasan S, Abidoye O, Fine GD, Dreicer R (2016) Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet (London, England) 387(10031):1909–1920. https://doi.org/10.1016/s0140-6736(16)00561-4

    Article  CAS  Google Scholar 

  12. Al Jarroudi O, Ulusakarya A, Almohamad W, Afqir S, Morere JF (2020) Anti-programmed cell death protein 1 (PD-1) immunotherapy for metastatic hepatocellular carcinoma after liver transplantation: a report of three cases. Cureus 12(10):e11150. https://doi.org/10.7759/cureus.11150

    Article  PubMed  PubMed Central  Google Scholar 

  13. Amara D, Wisel SA, Braun HJ, Collisson EA, Friedlander T, Worner G, Roll GR, Hirose R, Stock PG (2021) Metastatic donor-derived malignancies following simultaneous pancreas-kidney transplant: three case reports and management strategies. Transplant Dir 7(1):e636. https://doi.org/10.1097/txd.0000000000001090

    Article  Google Scholar 

  14. Amjad W, Kotiah S, Gupta A, Morris M, Liu L, Thuluvath PJ (2020) Successful treatment of disseminated hepatocellular carcinoma after liver transplantation with Nivolumab. J Clin Exp Hepatol 10(2):185–187. https://doi.org/10.1016/j.jceh.2019.11.009

    Article  PubMed  Google Scholar 

  15. Anugwom C, Leventhal T (2020) Nivolumab-induced autoimmune-like cholestatic hepatitis in a liver transplant recipient. ACG Case Rep J 7(7):e00416. https://doi.org/10.14309/crj.0000000000000416

    Article  PubMed  PubMed Central  Google Scholar 

  16. Barnett R, Barta VS, Jhaveri KD (2017) Preserved renal-allograft function and the PD-1 pathway inhibitor Nivolumab. N Engl J Med 376(2):191–192. https://doi.org/10.1056/NEJMc1614298

    Article  PubMed  Google Scholar 

  17. Biondani P, De Martin E, Samuel D (2018) Safety of an anti-PD-1 immune checkpoint inhibitor in a liver transplant recipient. Ann Oncol 29(1):286–287. https://doi.org/10.1093/annonc/mdx548

    Article  CAS  PubMed  Google Scholar 

  18. Boils CL, Aljadir DN, Cantafio AW (2016) Use of the PD-1 pathway inhibitor nivolumab in a renal transplant patient with malignancy. Am J Transpl Off J Am Soc Transpl Am Soc Transpl Surg 16(8):2496–2497. https://doi.org/10.1111/ajt.13786

    Article  CAS  Google Scholar 

  19. Braun M, Fuchs V, Kian W, Roisman L, Peled N, Rosenberg E, Friedel L (2020) Nivolumab induced hepatocanalicular cholestasis and liver rejection in a patient with lung cancer and liver transplant. J Thorac Oncol 15(9):e149–e150. https://doi.org/10.1016/j.jtho.2020.01.026

    Article  CAS  PubMed  Google Scholar 

  20. Cuenca AG, Rosales I, Lee RJ, Wu CL, Colvin R, Feldman AS, Efstathiou JA, Tolkoff-Rubin N, Elias N (2020) Resolution of a high grade and metastatic bk polyomavirus-associated urothelial cell carcinoma following radical allograft nephroureterectomy and immune checkpoint treatment: a case report. Transpl Proc 52(9):2720–2725. https://doi.org/10.1016/j.transproceed.2020.06.012

    Article  CAS  Google Scholar 

  21. Danesh MJ, Mulvaney PM, Murakami N, Riella LV, Silk AW, Hanna GJ, Schmults CD (2020) Impact of corticosteroids on allograft protection in renal transplant patients receiving anti-PD-1 immunotherapy. Cancer Immunol Immunother CII 69(9):1937–1941. https://doi.org/10.1007/s00262-020-02644-2

    Article  PubMed  Google Scholar 

  22. De Toni EN, Gerbes AL (2017) Tapering of immunosuppression and sustained treatment with nivolumab in a liver transplant recipient. Gastroenterology 152(6):1631–1633. https://doi.org/10.1053/j.gastro.2017.01.063

    Article  PubMed  Google Scholar 

  23. DeLeon TT, Salomao MA, Aqel BA, Sonbol MB, Yokoda RT, Ali AH, Moss AA, Mathur AK, Chascsa DM, Rakela J, Bryce AH, Borad MJ (2018) Pilot evaluation of PD-1 inhibition in metastatic cancer patients with a history of liver transplantation: the Mayo Clinic experience. J Gastrointest Oncol 9(6):1054–1062. https://doi.org/10.21037/jgo.2018.07.05

    Article  PubMed  PubMed Central  Google Scholar 

  24. Dueland S, Guren TK, Boberg KM, Reims HM, Grzyb K, Aamdal S, Julsrud L, Line PD (2017) Acute liver graft rejection after ipilimumab therapy. Ann Oncol 28(10):2619–2620. https://doi.org/10.1093/annonc/mdx281

    Article  CAS  PubMed  Google Scholar 

  25. Friend BD, Venick RS, McDiarmid SV, Zhou X, Naini B, Wang H, Farmer DG, Busuttil RW, Federman N (2017) Fatal orthotopic liver transplant organ rejection induced by a checkpoint inhibitor in two patients with refractory, metastatic hepatocellular carcinoma. Pediatr Blood Cancer. https://doi.org/10.1002/pbc.26682

    Article  PubMed  Google Scholar 

  26. Gassmann D, Weiler S, Mertens JC, Reiner CS, Vrugt B, Nägeli M, Mangana J, Müllhaupt B, Jenni F, Misselwitz B (2018) Liver allograft failure after nivolumab treatment-a case report with systematic literature research. Transplant Dir 4(8):e376. https://doi.org/10.1097/txd.0000000000000814

    Article  Google Scholar 

  27. Goldman JW, Abdalla B, Mendenhall MA, Sisk A, Hunt J, Danovitch GM, Lum EL (2018) PD 1 checkpoint inhibition in solid organ transplants: 2 sides of a coin—case report. BMC Nephrol 19(1):210. https://doi.org/10.1186/s12882-018-1003-5

    Article  PubMed  PubMed Central  Google Scholar 

  28. Grant MJ, DeVito N, Salama AKS (2018) Checkpoint inhibitor use in two heart transplant patients with metastatic melanoma and review of high-risk populations. Melanoma Manag 5(4):Mmt10. https://doi.org/10.2217/mmt-2018-0004

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gueguen J, Bailly E, Machet L, Miquelestorena-Standley E, Stefic K, Gatault P, Büchler M (2019) CMV disease and colitis in a kidney transplanted patient under pembrolizumab. Eur J Cancer (Oxford, England: 1990) 109:172–174. https://doi.org/10.1016/j.ejca.2018.12.027

    Article  Google Scholar 

  30. Hanna DL, Law SJ, Merrick SA, Heptinstall L, Bass P, Dupont P, Sheri A (2020) The successful use of pembrolizumab in a renal transplant recipient with metastatic melanoma. Melanoma Res 30(3):321–324. https://doi.org/10.1097/cmr.0000000000000651

    Article  CAS  PubMed  Google Scholar 

  31. Herz S, Höfer T, Papapanagiotou M, Leyh JC, Meyenburg S, Schadendorf D, Ugurel S, Roesch A, Livingstone E, Schilling B, Franklin C (2016) Checkpoint inhibitors in chronic kidney failure and an organ transplant recipient. Eur J Cancer (Oxford, England: 1990) 67:66–72. https://doi.org/10.1016/j.ejca.2016.07.026

    Article  Google Scholar 

  32. Hurkmans DP, Verhoeven J, de Leur K, Boer K, Joosse A, Baan CC, von der Thüsen JH, van Schaik RHN, Mathijssen RHJ, van der Veldt AAM, Hesselink DA (2019) Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment. J Immunother Cancer 7(1):182. https://doi.org/10.1186/s40425-019-0653-6

    Article  PubMed  PubMed Central  Google Scholar 

  33. Jose A, Yiannoullou P, Bhutani S, Denley H, Morton M, Picton M, Summers A, van Dellen D, Augustine T (2016) Renal allograft failure after ipilimumab therapy for metastatic melanoma: a case report and review of the literature. Transpl Proc 48(9):3137–3141. https://doi.org/10.1016/j.transproceed.2016.07.019

    Article  CAS  Google Scholar 

  34. Kumar V, Shinagare AB, Rennke HG, Ghai S, Lorch JH, Ott PA, Rahma OE (2020) The safety and efficacy of checkpoint inhibitors in transplant recipients: a case series and systematic review of literature. Oncologist 25(6):505–514. https://doi.org/10.1634/theoncologist.2019-0659

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Kuo JC, Lilly LB, Hogg D (2018) Immune checkpoint inhibitor therapy in a liver transplant recipient with a rare subtype of melanoma: a case report and literature review. Melanoma Res 28(1):61–64. https://doi.org/10.1097/cmr.0000000000000410

    Article  PubMed  Google Scholar 

  36. Le Fournis S, Gohier P, Urban T, Jeanfaivre T, Hureaux J (2016) Corneal graft rejection in a patient treated with nivolumab for primary lung cancer. Lung Cancer 102:28–29. https://doi.org/10.1016/j.lungcan.2016.10.008

    Article  PubMed  Google Scholar 

  37. Lipson EJ, Bagnasco SM, Moore J Jr, Jang S, Patel MJ, Zachary AA, Pardoll DM, Taube JM, Drake CG (2016) Tumor regression and allograft rejection after administration of anti-PD-1. N Engl J Med 374(9):896–898. https://doi.org/10.1056/NEJMc1509268

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lipson EJ, Bodell MA, Kraus ES, Sharfman WH (2014) Successful administration of ipilimumab to two kidney transplantation patients with metastatic melanoma. J Clin Oncol Off J Am Soc Clin Oncol 32(19):e69-71. https://doi.org/10.1200/jco.2013.49.2314

    Article  Google Scholar 

  39. Lipson EJ, Naqvi FF, Loss MJ, Schollenberger MD, Pardoll DM, Moore J Jr, Brennan DC (2020) Kidney retransplantation after anti-programmed cell death-1 (PD-1)-related allograft rejection. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 20(8):2264–2268. https://doi.org/10.1111/ajt.15856

    Article  Google Scholar 

  40. Medrano C, Vergez F, Mengelle C, Faguer S, Kamar N, Del Bello A (2019) Effectiveness of immune checkpoint inhibitors in transplant recipients with progressive multifocal leukoencephalopathy. Emerg Infect Dis 25(11):2145–2147. https://doi.org/10.3201/eid2511.190705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Mejia CD, Frank AM, Singh P, Yadav A (2020) Immune checkpoint inhibitor therapy-associated graft intolerance syndrome in a failed kidney transplant recipient. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg. https://doi.org/10.1111/ajt.16326

    Article  Google Scholar 

  42. Miller DM, Faulkner-Jones BE, Stone JR, Drews RE (2017) Complete pathologic response of metastatic cutaneous squamous cell carcinoma and allograft rejection after treatment with combination immune checkpoint blockade. JAAD Case Rep 3(5):412–415. https://doi.org/10.1016/j.jdcr.2017.06.005

    Article  PubMed  PubMed Central  Google Scholar 

  43. Morales RE, Shoushtari AN, Walsh MM, Grewal P, Lipson EJ, Carvajal RD (2015) Safety and efficacy of ipilimumab to treat advanced melanoma in the setting of liver transplantation. J Immunother Cancer 3:22. https://doi.org/10.1186/s40425-015-0066-0

    Article  PubMed  PubMed Central  Google Scholar 

  44. Ong M, Ibrahim AM, Bourassa-Blanchette S, Canil C, Fairhead T, Knoll G (2016) Antitumor activity of nivolumab on hemodialysis after renal allograft rejection. J Immunother Cancer 4:64. https://doi.org/10.1186/s40425-016-0171-8

    Article  PubMed  PubMed Central  Google Scholar 

  45. Owonikoko TK, Kumar M, Yang S, Kamphorst AO, Pillai RN, Akondy R, Nautiyal V, Chatwal MS, Book WM, Sahu A, Sica GL, Ahmed R, Ramalingam SS (2017) Cardiac allograft rejection as a complication of PD-1 checkpoint blockade for cancer immunotherapy: a case report. Cancer Immunol Immunother CII 66(1):45–50. https://doi.org/10.1007/s00262-016-1918-2

    Article  PubMed  Google Scholar 

  46. Padala SA, Patel SK, Vakiti A, Patel N, Gani I, Kapoor R, Muhammad S (2020) Pembrolizumab-induced severe rejection and graft intolerance syndrome resulting in renal allograft nephrectomy. J Oncol Pharm Pract Off Publ Int Soc Oncol Pharm Pract. https://doi.org/10.1177/1078155220934160

    Article  Google Scholar 

  47. Pandey A, Cohen DJ (2020) Ipilumumab for hepatocellular cancer in a liver transplant recipient, with durable response, tolerance and without allograft rejection. Immunotherapy 12(5):287–292. https://doi.org/10.2217/imt-2020-0014

    Article  CAS  PubMed  Google Scholar 

  48. Pluchart H, Ferrer L, Giovannini D, Tetaz R, Pinsolle J, Stephanov O, Giaj Levra M, Moro-Sibilot D, Toffart AC (2019) Concomitant use of nivolumab and immunosuppressants in a renal transplant patient. Rev Mal Respir 36(9):1064–1068. https://doi.org/10.1016/j.rmr.2019.08.004

    Article  CAS  PubMed  Google Scholar 

  49. Qin R, Salama AK (2015) Report of ipilimumab in a heart transplant patient with metastatic melanoma on tacrolimus. Melanoma Manag 2(4):311–314. https://doi.org/10.2217/mmt.15.27

    Article  PubMed  PubMed Central  Google Scholar 

  50. Rammohan A, Reddy MS, Farouk M, Vargese J, Rela M (2018) Pembrolizumab for metastatic hepatocellular carcinoma following live donor liver transplantation: the silver bullet? Hepatology (Baltimore, MD) 67(3):1166–1168. https://doi.org/10.1002/hep.29575

    Article  Google Scholar 

  51. Ranganath HA, Panella TJ (2015) Administration of ipilimumab to a liver transplant recipient with unresectable metastatic melanoma. J Immunother (Hagerstown, Md: 1997) 38(5):211. https://doi.org/10.1097/cji.0000000000000077

    Article  Google Scholar 

  52. Sadaat M, Jang S (2018) Complete tumor response to pembrolizumab and allograft preservation in renal allograft recipient on immunosuppressive therapy. J Oncol Pract 14(3):198–199. https://doi.org/10.1200/jop.2017.027326

    Article  PubMed  Google Scholar 

  53. Schvartsman G, Perez K, Sood G, Katkhuda R, Tawbi H (2017) Immune checkpoint inhibitor therapy in a liver transplant recipient with melanoma. Ann Intern Med 167(5):361–362. https://doi.org/10.7326/l17-0187

    Article  PubMed  Google Scholar 

  54. Singh P, Von Visger J, Prosek J, Rovin B, Pesavento TE, Olencki T, Pandey D (2019) Preserved renal allograft function and successful treatment of metastatic merkel cell cancer post nivolumab therapy. Transplantation 103(2):e52–e53. https://doi.org/10.1097/tp.0000000000002502

    Article  PubMed  Google Scholar 

  55. Soellradl I, Kehrer H, Cejka D (2020) Use of Ipilimumab and Pembrolizumab in metastatic melanoma in a combined heart and kidney transplant recipient: a case report. Transpl Proc 52(2):657–659. https://doi.org/10.1016/j.transproceed.2019.09.014

    Article  CAS  Google Scholar 

  56. Spain L, Higgins R, Gopalakrishnan K, Turajlic S, Gore M, Larkin J (2016) Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Ann Oncol 27(6):1135–1137. https://doi.org/10.1093/annonc/mdw130

    Article  CAS  PubMed  Google Scholar 

  57. Tio M, Rai R, Ezeoke OM, McQuade JL, Zimmer L, Khoo C, Park JJ, Spain L, Turajlic S, Ardolino L, Yip D, Goldinger SM, Cohen JV, Millward M, Atkinson V, Kane AY, Ascierto PA, Garbe C, Gutzmer R, Johnson DB, Rizvi HA, Joshua AM, Hellmann MD, Long GV, Menzies AM (2018) Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection. Eur J Cancer (Oxford, England: 1990) 104:137–144. https://doi.org/10.1016/j.ejca.2018.09.017

    Article  CAS  Google Scholar 

  58. Trager MH, Coley SM, Dube G, Khan S, Ingham M, Samie FH, Geskin LJ, McDonnell D, Brouder D, Saenger Y, Carvajal R (2020) Combination checkpoint blockade for metastatic cutaneous malignancies in kidney transplant recipients. J Immunother cancer. https://doi.org/10.1136/jitc-2020-000908

    Article  PubMed  PubMed Central  Google Scholar 

  59. Tsung I, Worden FP, Fontana RJ (2020) A pilot study of checkpoint inhibitors in solid organ transplant recipients with metastatic cutaneous squamous cell carcinoma. Oncologist. https://doi.org/10.1002/onco.13539

    Article  PubMed  PubMed Central  Google Scholar 

  60. Vahonsebrouck E, Van De Walle Mn E, Lybaert W, Kruse V, Roels D (2020) Bilateral corneal graft rejection associated with pembrolizumab treatment. Cornea 39(11):1436–1438. https://doi.org/10.1097/ico.0000000000002372

    Article  Google Scholar 

  61. Venkatachalam K, Malone AF, Heady B, Santos RD, Alhamad T (2020) Poor outcomes with the use of checkpoint inhibitors in kidney transplant recipients. Transplantation 104(5):1041–1047. https://doi.org/10.1097/tp.0000000000002914

    Article  PubMed  Google Scholar 

  62. Winkler JK, Gutzmer R, Bender C, Lang N, Zeier M, Enk AH, Hassel JC (2017) Safe administration of An anti-PD-1 antibody to kidney-transplant patients: 2 clinical cases and review of the literature. J Immunother (Hagerstown, Md: 1997) 40(9):341–344. https://doi.org/10.1097/cji.0000000000000188

    Article  CAS  Google Scholar 

  63. Wong K, Shen J, D’Ambruoso S, Stefanoudakis D, Drakaki A (2019) Safety and efficacy of immune checkpoint inhibitors in patients with metastatic cancer post solid organ transplantation: a case report and review of the literature. Transpl Proc 51(9):3053–3058. https://doi.org/10.1016/j.transproceed.2019.08.002

    Article  Google Scholar 

  64. Wu CK, Juang GD, Lai HC (2017) Tumor regression and preservation of graft function after combination with anti-PD-1 immunotherapy without immunosuppressant titration. Ann Oncol 28(11):2895–2896. https://doi.org/10.1093/annonc/mdx409

    Article  PubMed  Google Scholar 

  65. Zehou O, Leibler C, Arnault JP, Sayegh J, Montaudié H, Rémy P, Glotz D, Cordonnier C, Martin L, Lebbé C (2018) Ipilimumab for the treatment of advanced melanoma in six kidney transplant patients. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 18(12):3065–3071. https://doi.org/10.1111/ajt.15071

    Article  CAS  Google Scholar 

  66. Zhuang L, Mou HB, Yu LF, Zhu HK, Yang Z, Liao Q, Zheng SS (2020) Immune checkpoint inhibitor for hepatocellular carcinoma recurrence after liver transplantation. Hepatobiliary Pancreat Dis Int: HBPD INT 19(1):91–93. https://doi.org/10.1016/j.hbpd.2019.09.011

    Article  PubMed  Google Scholar 

  67. Nordness MF, Hamel S, Godfrey CM, Shi C, Johnson DB, Goff LW, O’Dell H, Perri RE, Alexopoulos SP (2020) Fatal hepatic necrosis after nivolumab as a bridge to liver transplant for HCC: Are checkpoint inhibitors safe for the pretransplant patient? Am J Transplant 20(3):879–883. https://doi.org/10.1111/ajt.15617

    Article  PubMed  Google Scholar 

  68. Dutra C, Garcia BR, Vieira R, Figueiredo AC, Néron Y (2019) EP1.04–32 successful corneal transplantation in a patient treated with nivolumab for metastatic non-small cell lung cancer. J Thorac Oncol 14(10):S981. https://doi.org/10.1016/j.jtho.2019.08.2155

    Article  Google Scholar 

  69. Kumar S (2019) Nivolumab-induced severe allograft rejection in recurrent post-transplant hepatocellular carcinoma. Am J Gastroenterol 114:S1251–S1252. https://doi.org/10.14309/01.ajg.0000598472.41771.5f

    Article  Google Scholar 

  70. Kwatra V, Karanth N, Priyadarshana K, Charakidis M (2016) Pembrolizumab for metastatic melanoma in renal allograft recipient with subsequent graft rejection and treatment response failure, a case report. Asia Pac J Clin Oncol 12:119–120

    Google Scholar 

  71. Lee BT, Han H, Chopra S, Aheam AJ (2019) Nivolumab-induced rejection of a liver allograft: PD-1 inhibition thwarts liver allograft resistance to humoral rejection. Am J Transplant 19:1077–1078. https://doi.org/10.1111/ajt.15406

    Article  Google Scholar 

  72. Verhoeven J, Hurkmans D, de Leur K, Boer K, Joosse A, Baan C, von der Thüsen J, Van Schaik R, Mathijssen R, Van Der Veldt A, Hesselink D (2019) Donor-derived cell-free DNA detects kidney transplant rejection during nivolumab treatment. Transpl Int 32:337

    Google Scholar 

  73. Chae BR, Kim YJ, Lee YS (2020) Prognostic accuracy of the sequential organ failure assessment (SOFA) and quick SOFA for mortality in cancer patients with sepsis defined by systemic inflammatory response syndrome (SIRS). Support Care Cancer Off J Multinatl Assoc Support Care Cancer 28(2):653–659. https://doi.org/10.1007/s00520-019-04869-z

    Article  Google Scholar 

  74. Vitale A, Morales RR, Zanus G, Farinati F, Burra P, Angeli P, Frigo AC, Del Poggio P, Rapaccini G, Di Nolfo MA, Benvegnù L, Zoli M, Borzio F, Giannini EG, Caturelli E, Chiaramonte M, Trevisani F, Cillo U (2011) Barcelona clinic liver cancer staging and transplant survival benefit for patients with hepatocellular carcinoma: a multicentre, cohort study. Lancet Oncol 12(7):654–662. https://doi.org/10.1016/s1470-2045(11)70144-9

    Article  PubMed  Google Scholar 

  75. Dietz AC, Seidel K, Leisenring WM, Mulrooney DA, Tersak JM, Glick RD, Burnweit CA, Green DM, Diller LR, Smith SA, Howell RM, Stovall M, Armstrong GT, Oeffinger KC, Robison LL, Termuhlen AM (2019) Solid organ transplantation after treatment for childhood cancer: a retrospective cohort analysis from the Childhood Cancer Survivor Study. Lancet Oncol 20(10):1420–1431. https://doi.org/10.1016/s1470-2045(19)30418-8

    Article  PubMed  PubMed Central  Google Scholar 

  76. Acuna SA, Huang JW, Daly C, Shah PS, Kim SJ, Baxter NN (2017) Outcomes of solid organ transplant recipients with preexisting malignancies in remission: a systematic review and meta-analysis. Transplantation 101(3):471–481. https://doi.org/10.1097/tp.0000000000001192

    Article  PubMed  Google Scholar 

  77. Acuna SA, Huang JW, Dossa F, Shah PS, Kim SJ, Baxter NN (2017) Cancer recurrence after solid organ transplantation: A systematic review and meta-analysis. Transplant Rev (Orlando) 31(4):240–248. https://doi.org/10.1016/j.trre.2017.08.003

    Article  Google Scholar 

  78. Gogna S, Ramakrishna K, John S (2020) Post transplantation cancer. In: StatPearls. StatPearls Publishing, Copyright© 2020, StatPearls Publishing LLC., Treasure Island

  79. Esfahani K, Al-Aubodah TA, Thebault P, Lapointe R, Hudson M, Johnson NA, Baran D, Bhulaiga N, Takano T, Cailhier JF, Piccirillo CA, Miller WH (2019) Targeting the mTOR pathway uncouples the efficacy and toxicity of PD-1 blockade in renal transplantation. Nat Commun 10(1):4712. https://doi.org/10.1038/s41467-019-12628-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Lichtenberg S, Rahamimov R, Green H, Fox BD, Mor E, Gafter U, Chagnac A, Rozen-Zvi B (2017) The incidence of post-transplant cancer among kidney transplant recipients is associated with the level of tacrolimus exposure during the first year after transplantation. Eur J Clin Pharmacol 73(7):819–826. https://doi.org/10.1007/s00228-017-2234-2

    Article  CAS  PubMed  Google Scholar 

  81. Saber-Moghaddam N, Nomani H, Sahebkar A, Johnston TP, Mohammadpour AH (2019) The change of immunosuppressive regimen from calcineurin inhibitors to mammalian target of rapamycin (mTOR) inhibitors and its effect on malignancy following heart transplantation. Int Immunopharmacol 69:150–158. https://doi.org/10.1016/j.intimp.2019.01.035

    Article  CAS  PubMed  Google Scholar 

  82. He J, Li Y, Zhang H, Wei X, Zheng H, Xu C, Bao X, Yuan X, Hou J (2013) Immune function assay (ImmuKnow) as a predictor of allograft rejection and infection in kidney transplantation. Clin Transplant 27(4):E351-358. https://doi.org/10.1111/ctr.12134

    Article  PubMed  Google Scholar 

  83. d’Izarny-Gargas T, Durrbach A, Zaidan M (2020) Efficacy and tolerance of immune checkpoint inhibitors in transplant patients with cancer: a systematic review. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 20(9):2457–2465. https://doi.org/10.1111/ajt.15811

    Article  Google Scholar 

  84. Seidel JA, Otsuka A, Kabashima K (2018) Anti-PD-1 and Anti-CTLA-4 therapies in cancer: mechanisms of action, efficacy, and limitations. Front Oncol 8:86. https://doi.org/10.3389/fonc.2018.00086

    Article  PubMed  PubMed Central  Google Scholar 

  85. Petrelli F, Ghidini M, Ghidini A, Tomasello G (2020) Outcomes following immune checkpoint inhibitor treatment of patients with microsatellite instability-high cancers: a systematic review and meta-analysis. JAMA Oncol 6(7):1068–1071. https://doi.org/10.1001/jamaoncol.2020.1046

    Article  PubMed  Google Scholar 

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Supplementary file1 Table. S1: Multivariate logistic regression (XLSX 11 kb)

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Miao, K., Zhang, L. Application of Immune Checkpoint Inhibitors in Solid Organ Transplantation Recipients: A Systematic Review. Interdiscip Sci Comput Life Sci 13, 801–814 (2021). https://doi.org/10.1007/s12539-021-00437-4

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