Dendritic cells from patients with myeloma are numerically normal but functionally defective as they fail to up-regulate CD80 (B7-1) expression after huCD40LT stimulation because of inhibition by transforming growth factor-β1 and interleukin-10

Limited response to idiotype vaccination in patients with myeloma suggests that there is a need to develop better immunotherapy strategies. It has been determined that the number of high-potency CMRF44(+)CD14(-)CD19(-) dendritic cells (DCs) in the blood of patients with myeloma (range, 0.03%-0.8% of mononuclear cells [MNCs]; n = 26) was not significantly different from that in controls (range, 0.05%-0.8% of MNCs; n = 13). Expression of the costimulatory molecules CD80 and CD86 on DCs from these patients (mean, 29% +/- 17% of MNCs and 85% +/- 10% of MNCs, respectively) was also normal (mean, 29% +/- 17% and 86% +/- 16% of MNCs, respectively). Up-regulation of CD80 expression in response to stimulation by human (hu)CD40LT + interleukin (IL)-2 was significantly reduced on the DCs of patients with myeloma during stable disease (n = 9) and was absent during progressive stages (n = 7) of disease. Similar effects were seen on B cells but not on monocytes of the same group of patients. CD86 expression on DCs was high before (86%) and after (89%) stimulation. Inhibition of CD80 up-regulation was neutralized by either anti-transforming growth factor (TGF)-beta (1) or anti-IL-10. Upregulation of CD80 on DCs of controls was inhibited by rTGF-beta (1) in a dose-dependent manner. Serum TGF-beta (1) and IL-10 levels were normal in most patients studied. Cytoplasmic TGF-beta (1) was increased in plasma cells during progressive disease. Thus patients With myeloma have normal numbers of DCs, but CD80 expression may fail to be up-regulated in the presence of huCD40LT because of tumor-derived TGF-P, or IL-10. Autologous high-potency DCs may have to be tested for CD80 up-regulation and biologically modified ex vivo before idiotype priming for immunotherapy. (C) 2001 by The American Society of Hematology.