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Fig. 1. (A) Mechanism of action of immune checkpoint inhibitors (ICIs). When programmed cell death protein 1 (PD-1) on T cells binds to programmed cell death ligand 1 (PD-L1) or 2 on cancer cells or antigen-presenting cells, T cell activation is suppressed, causing immune escape of cancer cells. Anti-PD-1 antibodies bind to PD-1 on T cells and inhibit the binding of PD-1 to PD-L1/PD-L2, thereby blocking the transmission of inhibitory signals, maintaining T cell activation and restoring the anti-tumor effect. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is expressed on activated T cells and Treg cells, and inhibits T cell activation by binding to B7 on antigen-presenting cells. By inhibiting the binding of CTLA-4 to B7, the anti-CTLA-4 antibody enables the binding of CD28 to B7, thereby reactivating T cells. (B) Mechanism of rejection caused by ICIs. In posttransplant patients, donor cells produce donor antigens, and immunosuppressants are used to suppress T cell activation and regulate immunological tolerance. In patients with cancer after organ transplant, a reduction in the dose of immunosuppressants is often considered to avoid overimmunosuppression and to recover adequate tumor immunity. In addition, ICIs have the potential to disrupt the equilibrium of immunological tolerance and lead to acute rejection. MHC, major histocompatibility complex; TCR, T-cell receptor; LAG3, lymphocyte activation gene 3; CNI, calcineurin inhibitor; MMF, mycophenolate mofetil; mTORi, mammalian target of rapamycin inhibitor.
Korean J Transplant 2022;36:82~98
© Korean J Transplant