Immunomodulatory effect of NEDD8-activating enzyme inhibition in Multiple Myeloma: upregulation of NKG2D ligands and sensitization to Natural Killer cell recognition.

ABSTRACT: Multiple Myeloma (MM) is an incurable hematologic malignancy of terminally differentiated plasma cells (PCs), where immune interactions play a key role in the control of cancer cell growth and survival. In particular, MM is characterized by a highly immunosuppressive bone marrow microenvironment where the anticancer/cytotoxic activity of Natural Killer (NK) cells is impaired. This study is focused on understanding whether modulation of neddylation can regulate NK cell-activating ligands expression and sensitize MM to NK cell killing. Neddylation is a post-translational modification that adds a ubiquitin-like protein, NEDD8, to selected substrate proteins, affecting their stability, conformation, subcellular localization, and function. We found that pharmacologic inhibition of neddylation u

SUBMITTER: Petillo S 

PROVIDER: S-EPMC8418610 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature