Immunoregulation of murine and human myeloma

The studies presented in this review address the issue of immunoregulation of growth and differentiation of myeloma tumor cells by host effector cells (Fig. 1). In the murine myeloma system, substantial, direct evidence is presented that myeloma tumor cell growth and differentiation can be modulated by host idiotype-, antigen-, and isotype-specific immunoregulatory cells. Only isotype-specific immunoregulatory cells, however, represent an endogenous, host-generated response, whereas idiotype- and antigen-specific responses require exogenous manipulation (immunization) of the host. In patients with multiple myeloma, however, little direct evidence is available showing regulation of growth and differentiation of tumor cells. Instead, a substantial body of literature suggests a complex interaction between the host immune system and the tumor that, in principle, may result in regulation of tumor cell growth and/or differentiation, although at best the regulation is clinically ineffective. Changes in the phenotype and functions of T cells, B cells, macrophages, and NK/LAK cells have been demonstrated in patients with multiple myeloma and, at least in vitro, each of these cell populations has been shown to modulate growth/differentiation or survival of human myeloma cells. The future challenge in our studies of the immunobiology of multiple myeloma will be to better understand the mechanisms controlling growth of myeloma tumor cells and the interactions between the tumor cells and the host immune system so that we might develop appropriate strategies to augment antitumor immune responses.