Toll-Like Receptors in Human Multiple Myeloma: New Insight into Inflammation-Related Pathogenesis

Multiple myeloma (MM) is a clonal neoplasm characterized by expansion of malignant plasma cells in the bone marrow causing various complications including osteolytic lesions and impaired immune function. It has recently been reported that human myeloma cells express multiple Toll-like receptors (TLRs), and their activation-induced functional responses show heterogeneity among cell lines and patient samples. TLRs are critical germ-line encoded molecules expressed in immune cells as well as in a variety of cancer cells. In multiple myeloma, they may induce cell growth and proliferation or promote cell death. In fact, our current knowledge of Toll-like receptor function has gone beyond their main function as triggers of innate and adaptive immune responses. Considering the essential role of bone marrow microenvironment components in myeloma tumor expansion, survival, invasion and drug resistance, TLR triggering may contribute to adhesion-induced or de novo drug resistance of MM cells. Future preclinical and clinical studies are needed to address if TLRs can be exploited as novel therapeutic targets for MM.