title: Targeting multiple-myeloma-induced immune dysfunction to improve immunotherapy outcomes.
abstract: Multiple myeloma (MM) is a plasma cell malignancy associated with high levels of monoclonal (M) protein in the blood and/or serum. MM can occur de novo or evolve from benign monoclonal gammopathy of undetermined significance (MGUS). Current translational research into MM focuses on the development of combination therapies directed against molecularly defined targets and that are aimed at achieving durable clinical responses. MM cells have a unique ability to evade immunosurveillance through several mechanisms including, among others, expansion of regulatory T cells (Treg), reduced T-cell cytotoxic activity and responsiveness to IL-2, defects in B-cell immunity, and induction of dendritic cell (DC) dysfunction. Immune defects could be a major cause of failure of the recent immunotherapy trials in MM. This article summarizes our current knowledge on the molecular determinants of immune evasion in patients with MM and highlights how these pathways can be targeted to improve patients' clinical outcome.
authors.affiliation: Department of Pediatric Hematology/Oncology, IRCCS Bambino Gesù Children's Hospital, Piazza Sant'Onofrio 4, 00165 Rome, Italy. srutella@rm.unicatt.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007156:Immunologic Memory; D007167:Immunotherapy; D009101:Multiple Myeloma / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D058996:Quality Improvement; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D016896:Treatment Outcome; D019139:Tumor Escape