NKG2D and DNAM-1 Ligands: Molecular Targets for NK Cell-Mediated Immunotherapeutic Intervention in Multiple Myeloma

Figure 1

Drug-activated pathways regulating NK cell activating ligand expression. Hsp90 inhibitors regulate MICA/B expression via HSF1 activation. Drugs targeting GSK-3 repress STAT3 leading to MICA upregulation. Genotoxic drugs induce the expression of NKG2D or DNAM-1 ligands following the activation of DDR-dependent E2F1 transcription factor. Proteasome inhibitors induce MICA expression via ATM and Chk-2 activation. HDAC inhibitors increase MICA/B and ULBP2 levels with a mechanism dependent on ERK activation. Molecules or pathways not involved in the regulation of these ligands are indicated in grey color and with dotted raw.