The survival of multiple myeloma cells depends heavily on interactions with other cells in the bone marrow. These interactions represent potentially new targets for treatment. However, the specific molecules involved in these interactions are largely unknown. We have found that CD28 (a receptor found primarily on T cells) is also expressed on myeloma cells, and protects these cells against killing by certain chemotherapy agents. The goals of this proposal are to characterize how CD28 supports myeloma cell survival, and assess if targeting CD28 itself and/or components of it's signaling pathway can be developed for treatment.