Immune checkpoint inhibitors in the management of malignancies in transplant recipients

Abstract

Cancer immunotherapy, an area of active research, has thus far yielded several exciting breakthroughs in cancer treatment strategies. So far, immune checkpoint inhibitors have been the most promising method of cancer immunotherapy. CTLA-4, PD-1 and PD-L1 are the immune checkpoint molecules against which monoclonal antibodies act against and revolutionised the treatment of several malignancies. However, it is still unclear whether using these monoclonal antibodies in patients with malignancy and a history of transplant is as beneficial as in patients without a history of transplantation. The reason being, with the therapeutic benefit, also comes the inherent disadvantage of transplant rejection because of the activation of T-cells against donor antigens. So, transplant-related complications limit the usage of the checkpoint blockade therapy to treat malignancies. Here, we review the data published in this context and suggest optimal approaches to using the currently available repertoire of immunotherapies.

Programmed Cell Death 1 (PD-1) Inhibitors in Renal Transplant Patients with Advanced Cancer: A Double-Edged Sword?

“…Moreover, no data regarding the use of PD-L1 inhibitors, such as atezolizumab, avelumab, or durvalumab, in renal transplant patients are available. Finally, evidence suggests that anti-CTLA4 monoclonal antibodies are associated with a lower risk of rejection in renal transplant recipients compared with anti-PD-1 monoclonal antibodies [5,6,7]. By reviewing the usage of PD-1 inhibitors in renal transplant recipients with advanced cancer, we attempted to provide possible factors that influence the efficacy and safety of these inhibitors.…”

Intratumoral immunotherapy with anti-PD-1 and TLR9 agonist induces systemic antitumor immunity without accelerating rejection of cardiac allografts

“…16 As such, minimizing or withdrawal of immunosuppression is necessary for anti-tumor immunotherapy in transplant patients to be fully effective. 11,16,33,34 Data from our present study provide a new concept that immune tolerance to an organ allograft induced, at least tem- anti-tumor response, potentially addressing intra-and intertumoral heterogeneity. [37][38][39][40] Despite being uncertain of the dominant epitopes of a given cancer, we can develop therapeutic strategies to trigger an immune response against the relevant neo-antigens or tumor-associated antigens without the need for their characterization.…”

“…Evidence has accumulated demonstrating that the reduced effect of the tumor immunotherapy is related to immunosuppressive conditions 16 . As such, minimizing or withdrawal of immunosuppression is necessary for anti‐tumor immunotherapy in transplant patients to be fully effective 11,16,33,34 . Data from our present study provide a new concept that immune tolerance to an organ allograft induced, at least temporarily, by a regimen containing for example PI4Ki, may allow for effective tumor immunotherapy.…”

“…19,20 This explains the limited anti-cancer effect of checkpoint blockades in transplanted patients under immunosuppression. 11,33,34 Evidence has accumulated demonstrating that the reduced effect of the tumor immunotherapy is related to immunosuppressive conditions. 16 As such, minimizing or withdrawal of immunosuppression is necessary for anti-tumor immunotherapy in transplant patients to be fully effective.…”

“…immunotherapy through mechanisms to unleash tumor reactive T cells from tumor‐associated immune inhibition and increased interaction between immune cells including APCs and T cells and development of effector CTLs 19,20 . This explains the limited anti‐cancer effect of checkpoint blockades in transplanted patients under immunosuppression 11,33,34 . Evidence has accumulated demonstrating that the reduced effect of the tumor immunotherapy is related to immunosuppressive conditions 16 .…”