Anti-CD14 Antibody [MEM-15] (FITC) (A85585)

Myeloid-derived suppressor cells (MDSCs) have been identified in the majority of patients and experimental mice with tumors by their suppression of T cell activation. MDSCs have also been reported to be associated with chronic inflammation. In advanced cancer, the T helper (Th) cell balance tends to shift from Th1 to Th2 predominance, and immune function, including cell-mediated immunity, is impaired by cytokines produced by Th2 cells. The present study examined the correlations between MDSC levels and inflammation, immune suppression, malnutrition, and poor prognosis in 155 patients with breast cancer. The levels of MDSCs in preoperative patients and in patients with recurrent breast cancer were significantly higher compared with postoperative patients, patients with recurrent breast cancer who received chemotherapy and healthy volunteers. The MDSC levels of preoperative patients were significantly positively correlated with interleukin (IL)-6 production by peripheral blood mononuclear cells (PBMCs), the neutrophil/lymphocyte ratio and C-reactive protein, and were negatively correlated with the production of interferon-γ and IL-12, serum concentration of rapid turnover protein, and the stimulation index. These patients were divided into two groups based on the levels of MDSCs. In preoperative patients with MDSC levels >1.0% of total PBMCs, the overall survival of patients with stage IV disease was significantly shorter compared with other disease stages, and was also significantly shorter compared with patients with MDSC levels <1.0% of total PBMCs. Thus, the MDSC levels of preoperative patients may function as a good prognostic indicator, particularly in patients with advanced breast cancer.

Giant cell tumor of bone (GCTB) is a benign, locally destructive neoplasm, with tumors comprised of mesenchymal fibroblast-like stromal cells; monocytic, mononuclear cells of myeloid lineage; and the characteristic osteoclast-like, multinucleated giant cells. Hampering the study of the complex interaction of its constituent cell types is the propensity of longstanding, repeatedly passaged cell cultures to undergo phenotypic alteration and loss of osteoclast-inducing capacities. In this study, we employed a novel, single-step technique to purify freshly harvested stromal cells using a CD14-negative selection column. Using 9 freshly harvested GCTB specimens and the purified stromal cell component, we performed analyses for markers of osteoblast lineage and analyzed the capacity of the stromal cells to undergo osteoblastic differentiation and induce osteoclastogenesis in co-cultures with monocytic cells. Successful purification of the CD14-negative stromal cells was confirmed via flow cytometric analysis and immunocytochemistry. Osteogenic media upregulated the expression of osteocalcin, suggesting an osteoblastic lineage of the GCTB stromal cells. The effects of the Wnt pathway agonist, SB415286, and recombinant human bone morphogenetic protein (BMP)-2 on osteoblastogenesis varied among samples. Notably, osteogenic media and SB415286 reversed the receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) expression ratio resulting in diminished osteoclastogenic capacity. Recombinant human BMP2 had the opposite effect, resulting in enhanced and sustained support of osteoclastogenesis. Targeting the giant cell tumor stromal cell may be an effective adjunct to existing anti-resorptive strategies.