Multiple myeloma is a malignant proliferation of plasma cells. At present, the disease remains essentially incurable and overall patient survival has improved only modestly over 30 years. We have provided evidence for a functional defect in the cells presenting tumor antigens in some patients with myeloma, and aimed to resolve the defect by upregulation of costimulatory molecules on these cells. To build upon our previous studies and findings, we intend to follow a number of separate but ultimately integrated paths. These lines of investigation may then lead to the understanding of the fundamental problems hindering effective immunotherapy in multiple myeloma.