PMC5937056_01
Summary of immunotherapy drugs or treatment strategies in NK/T cell lymphoma and their respective cellular membrane targets. Antibody drugs target cellular membrane proteins, which include Brentuximab/CD30 and Daratumumab/CD38. Engineered chimeric antigen T-cells are targeted toward CD30 much like Brentuximab. Anti-PD1 antibodies, such as Pembrolizumab and Nivolumab, target microenvironment T-cells that become inactivated when bound with Programmed death-ligand 1 (PD-L1) expressed on tumor cells, inducing anergy. Latent membrane protein 1 (LMP1) is a transmembrane protein produced by Epstein-Barr virus (EBV), which subsequently activates the NF-kappaB pathway and leads to cell proliferation and lymphomagenesis. This in turn upregulates PD-L1, which makes immune checkpoint blockade an attractive target. Furthermore, LMP1 antigen is expressed within a MHC-complex on the cell surface to which activated T cells can then recognize and extinguish. This was an originally produced image.
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F1
As EBV contributes to the pathogenesis of ENKTCL, expression of the immunogenic latent membrane protein 1 (LMP1) by the virus acts to enhance PD-L1 expression through upregulation of the MAPK/NF-kappaB pathways (Figure 1).