Immune checkpoint inhibitors for solid organ transplant recipients: clinical updates

Abstract

Transplant care continues to advance with increasing clinical experience and improvements in immunosuppressive therapy. As the population ages and long-term survival improves, transplant patient care has become more complex due to comorbidities, frailty, and the increased prevalence of cancer posttransplantation. Immune checkpoint inhibitors (ICIs) have become a standard treatment option for many cancers in non-transplant patients, but the use of ICIs in transplant patients is challenging due to the possibility of disrupting immune tolerance. However, over the past few years, ICIs have gradually started to be used in transplant patients as well. In this study, we review the current use of ICIs after all solid organ transplantation procedures (kidney, liver, heart, and lung). Increasing data suggest that the type and number of immunosuppressants may affect the risk of rejection after immunotherapy. Immunotherapy for cancer in transplant patients may be a feasible option for selected patients; however, prospective trials in specific organ transplant recipients are needed.

Immune checkpoint inhibitors in malignancies after liver transplantation: Better safe or sorry?

“…Importantly, amongst the cases that had received ICI before LT five patients had an acute rejection in the early post-transplant time. 9 It has been hypothesized that the lower incidence of acute rejection during ICI's therapy in LT compared to kidney transplant recipients might be associated with the inherent tollerogenicity of LT. Currently, clinical trials investigating the role of ICIs in recurrent HCC after LT are ongoing (Clini calTr ials.gov: NCT03966209 and NCT04564313).…”

“…The combination of ICIs has become the backbone for HCC systemic treatment and is currently recommended as the first line of treatment for advanced HCC. 6 Importantly, ICIs use before LT registration and during the waiting period have been described and there has been an increasing number of case reports of ICIs use in patients with HCC recurrence after LT. [7][8][9] Kawashima reported a recent review including 42 HCC patients, of which 22 cases were treated with ICIs after LT and 20 prior to LT. In the post-LT series, rejection was reported in five cases, whilst six patients showed a response to treatment.…”

Immune checkpoint inhibitors in kidney transplantation

“…Therefore, immunosuppressive agents, including antithymocyte globulin, basiliximab, glucocorticoids, calcineurin inhibitors (CNIs), mammalian target of rapamycin (mTOR) inhibitors, antimetabolites and co-stimulation blockers, are typically used as part of a combination regimen to prevent allograft rejection. As the graft is accepted, the initial vigorous immunosuppressive therapy is gradually tapered to a less intense maintenance immunosuppressive regimen, which is continued for the rest of the patient's life [9 ▪ ,15–17].…”

“…One risk factor is the higher susceptibility to infections by carcinogenic viruses, including Epstein--Barr, human herpes viruses and hepatitis C virus, which can cause posttransplant lymphoproliferative disease, anogenital carcinoma, Kaposi sarcoma, gastric and liver cancer, respectively. Another risk factor is that immune surveillance of cancerous cells is hampered by immunosuppressive therapy, which prevents the T cells from detecting neoantigens expressed on cancer cells and eliminating them [9 ▪ ].…”

“…The primed T cells recognize the cancer cells by these antigens and destroy them. However, some cancers express protein ligands on their membrane surfaces, which bind to the co-inhibitory checkpoint receptors such as CTLA-4, PD-1, TIGIT, LAG-3, on the surface of the T cells and inhibit them, resulting in immune evasion [9 ▪ ,26–28]. The mechanism is illustrated on Fig.…”