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

Abstract

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%)

Non-erythroid activities of erythropoietin: Functional effects on murine dendritic cells

“…Furthermore, DCs are inhibited in MM patients by cytokines that are secreted by the neoplastic plasma cells (Brown et al, 2001). This phenomenon is one of the major defects of the immune system observed in MM patients.…”

Laboratory Characterizations on 2007 Cases of Monoclonal Gammopathies in East China

“…A better understanding of any defects in the immune response in these patients is required before effective therapeutic strategies can be developed (24). Several studies supported that myeloma tumor cells in MM, the most common disease type in monoclonal gammopathies, evaded the immune system and could induce immunosuppression by producing immunoregulatory factors such as TGFβ1 (25). Myeloma cells increase Th3 cytokine response by secreting TGFβ1, which causes defective Th1 and Th2 cytokine responses, therefore a significant suppression of the immune system is seen (26).…”

Hypersensitivity pneumonitis

“…T-regulatory cells have the capacity to actively suppress the proliferation of naı¨ve CD4 + T cells by secreting IL-10 and TGF-b, two effective immunosuppressive cytokines (149). These cytokines can, in turn prevent dendritic cells maturation (150). An increased number of Treg cells could explain the tolerant response observed in mice subjects.…”