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Clinical and Developmental Immunology
Volume 2012 (2012), Article ID 196063, 13 pages
http://dx.doi.org/10.1155/2012/196063
Review Article

Targeting Multiple-Myeloma-Induced Immune Dysfunction to Improve Immunotherapy Outcomes

1Department of Pediatric Hematology/Oncology, IRCCS Bambino Gesù Children’s Hospital, Piazza Sant’Onofrio 4, 00165 Rome, Italy
2Catholic University Medical School, 00168 Rome, Italy
3University of Pavia, 27100 Pavia, Italy

Received 30 October 2011; Revised 12 January 2012; Accepted 29 January 2012

Academic Editor: Arnon Nagler

Copyright © 2012 Sergio Rutella and Franco Locatelli. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.