Immune regulation in multiple myeloma: the host–tumour conflict

Multiple myeloma (MM) remains essentially incurable by conventional anti-tumour therapy. This has led to increased interest in the possibility that forms of immune therapy might be effective. The successful use of donor lymphocyte infusions (DLI) in a few cases of MM relapse following allogeneic bone marrow transplantation have added weight to this view. MM is characterized by several defects in the host’s immune system. The influence of the malignant clone on the function of the immune effector cells results from both passive and active suppression. Despite an array of functional adhesion molecules and HLA class I and II molecules on their surface and the secretion of a tumour-specific peptide, they fail to express adequate levels of co-stimulatory molecules thus inducing anergy in potentially tumour-specific T cells. In addition to this passive evasion of immune regulation, MM tumour cells are capable of producing a number of immunologically active agents which can induce immunosuppression such as transforming growth factor-beta, Fas ligand (FasL), vascular endothelial growth factor and Muc-1. It is postulated that these agents may be produced by the tumour cell to influence the microenvironment to support growth and differentiation of the clone but may have the additional benefit of altering the function of the host immune effector cells and thus preventing tumour rejection. This duality of function is important if clinicians are to design immunotherapy strategies which will achieve the true potential and result in improved survival in MM.