Regulatory T cells and multiple myeloma

Many clinical observations point to active immunologic phenomena in patients with myeloma. These consist of active suppression of the host's immune system and partially successful attempts by the host's immune system to suppress the malignant B-cell population. Clinical conditions such. as asymptomatic myeloma, which represents clinical presentation in the plateau phase of the disease, plateau establishment after conventional induction therapy without the ongoing need for therapy, and the positive prognostic importance of the presence of clones of cytotoxic T cells in the peripheral blood of some patients, suggest that host-tumor interaction is an active dynamic state. Regulatory T (Treg) cells comprise 5%-10% of peripheral CD4 T cells and are responsible for the control of autoimmune phenomena. Deficiency of the FoxP3 transcription factor, which normally characterizes Treg cells, leads to multiorgan autoimmune disorders in humans and mice. The role of Treg cells in the protection from malignancy is unclear, but their depletion can lead to the induction of tumor rejection in murine models, and their demonstration as tumorinfiltrating lymphocytes in malignancy point to a significant immunomodulator role. In myeloma, host-tumor immune interactions are complex. However, patients can clearly exhibit control of their B-cell malignancy for many years with stability of paraprotein levels, demonstrating a homeostasis between tumor and host. Whether Treg cells are playing a role in this homeostasis is unclear. At present, there is considerable debate in the literature regarding observations such as whether Treg cells are increased or decreased, functional or dysfunctional. In this review, we will discuss the potential importance of Treg cells and their role in myeloma, a disease characterized by a unique set of host-tumor interactions.