Immunotherapies and Renal Injury

Abstract

Cancer immunotherapy represents a giant leap forward in the management of malignant diseases. An optimal anti-tumor immune response requires cancer antigen recognition by T-cells followed by an effector immune response. Suppression of T-cell activation prevents cancer cell clearance resulting in tumor proliferation. Recent clinical successes of immune checkpoint inhibitors and chimeric antigen receptor T cell therapies has transformed the landscape of cancer immunotherapy. The goal of immunotherapy is to boost host-protective anti-tumor immunity without concomitantly causing immune-related adverse events. However, immunotherapies can cause multiorgan dysfunction including acute kidney injury. Prompt recognition and management of immunotherapy-associated kidney injury is critical in preserving kidney function and improving patient outcomes.

Keywords: Acute kidney injury; Chimeric antigen receptor T cell therapy; Glomerular disease; Immune checkpoint inhibitor; Immunotherapy.

Figure 1.

1A. Cell-surface ligands involved in T-cell activation and T-cell inhibition. TCR-MHC engagement, followed by binding of the B7 ligand to the co-stimulatory CD28 receptor on T-cell surface leads to T-cell activation. Binding of the B7 ligand to CTLA-4 or binding of the PD-L1 ligand to PD-1 inhibits T cell activation. 1B. Site of action for anti-CTLA4, anti-PD-1 and anti-PD-L1 antibodies. Abbreviations: TCR: T cell receptor; MHC: major histocompatibility complex; CTLA-4: cytotoxic T cell associated lymphocyte antigen 4; PD-L1: programmed death ligand 1; PD-1: programmed death receptor 1.

Figure 2.

Overview of Chimeric Antigen Receptor T cell (CAR-T) therapy. CAR-T cells are manufactured by obtaining peripheral T-cells from the patient by leukapheresis followed by genetic engineering of T cells which involves insertion of the fusion protein CAR via a viral vector. This is followed by expansion of the CAR-T cells ex vivo. Lymphocyte depleting preconditioning chemotherapy is administered to the patient following which the CAR-T cells are infused into the patient. CAR-T cells recognize the tumor antigens on the cancer cells and attack the cancer cells.