Upregulation Of Pd-L1 On Myeloma Cells By Immunomodulatory Agents Potentiates The Effect Of Durvalumab

Introduction: Programmed death-ligand 1 (PD-L1) shows increased expression on plasma cells from multiple myeloma (MM) patients as compared with those from monoclonal gammopathy of undetermined significance patients and healthy volunteers. PD-L1 inhibits tumor-specific cytotoxic T lymphocyte-mediated responses via interaction with PD-1. Our previous study showed that PD-L1 on MM cells is associated with aggressive myeloma behaviors including cell proliferation and drug resistance, and furthermore the interaction of PD-L1 with PD-1 molecules induced drug resistance in MM cells by antiapoptotic responses through the Akt signaling pathway (Tamura et al. Leukemia 2013, Cancer Immunol Res 2016). We next investigated the regulation of PD-L1 expression by immunomodulatory drugs (IMDs) and antimyeloma effects of the anti-PD-L1 antibody durvalumab (DUR) in combination with IMDs.