Role of toll-like receptors in multiple myeloma and recent advances

Abstract

Multiple myeloma (MM) is a hematologic malignancy characterized as an abnormal proliferation and invasion of plasma cells into the bone marrow. Toll-like receptors (ТLRs) connect the innate and adaptive immune responses and represent a significant and potentially linking element between inflammation and cancer. When TLRs bind to their ligands, they trigger two major signaling pathways such that both share overlapping downstream signals: one is a myeloid differentiation primary response 88 (MyD88)-dependent production and activation of nuclear factor-κB, whereas the other is a MyD88-independent production of type-I interferon. Whereas the MyD88 pathway results in proinflammatory cytokine production, the other pathway stimulates cell proliferation. Dysregulations of these pathways may eventually lead to abnormal cell proliferation and MM. Despite recent biomedical advances, MM continues to be an incurable disease. There are an increasing number of TLR-based therapeutic approaches currently being tested in a number of preclinical and clinical studies. We here attempt to outline in detail the currently available information on TLRs in various types of cancer.