Immune Checkpoint Molecules in Solid Organ Transplantation: a Promising Way to Prevent Rejection

Immune checkpoint (IC) molecules modulate immune responses upon antigen presentation; the interaction between different IC molecules will result in the stimulation or, rather, the thwarting of such responses. Tumor cells express increased amounts of inhibitory IC molecules in an attempt to evade immune responses; therapeutic agents have been developed that bind inhibitory IC molecules, restoring tumor-directed immune responses and changing the prognosis of a number of cancers. Stimulation of inhibitory IC molecules could be beneficial in preventing rejection in the setting of solid organ transplantation (SOT), and in vivo as well as in vivo results obtained in animal models show this to indeed to be the case. With the exception of belatacept, a monoclonal antibody (mAb) in which an IgG Fc fragment is linked to the extracellular domain of CTLA-4, this has not yet translated into the generation of novel therapeutic approaches to prevent SOT rejection. We provide a review of state-of-the art knowledge on the role played by IC molecules in transplantation, confident that innovative research will lead to new avenues to manage rejection in solid organ transplant.