CD63 and plasma cell myeloma: In this study, we tested the hypothesis that hypoxia promotes increased CD63 expression in myeloma cells, which leads to enhanced exosome secretion and elevated lactate levels, leads to the polarization of M2 macrophages and the exhaustion of T cells by combining molecular, cellular, and immunological strategies, we aimed to elucidate this novel immunosuppressive mechanism involving lactate shuttling under hypoxia-induced CD63 upregulation and to identify potential therapeutic targets for reversing this process.