Effect of γδ T cells on the Proliferation, Apoptosis and Autophagy of Multiple Myeloma Cells / 中国实验血液学杂志

AbstractObjective: To investigate the effect of γδ T cells on the proliferation, apoptosis and autophagy of multiple myeloma cells.@*METHODS@#Peripheral blood mononuclear cells (PBMNC) were isolated from healthy volunteers, and stimulated with zoledronic acid (Zol) in combination with rhIL-2. Flow cytometry analysis was used to detected the purity of γδ T cells. γδ T cells were collected and co-cultured with RPMI-8226 or U-266 cells at different effector target ratios. The proliferation of RPMI-8226 or U-266 cell lines were detected by CCK-8. Cell cycle and cell apoptosis were detected by flow cytometry and Western blot．The expressions of autophagy-related proteins were detected by Western blot.@*RESULTS@#γδ T cells can be expanded in vitro. γδ T cells could inhibit the proliferation of RPMI-8226 or U-266 cells, induced cell cycle arrest and promoted apoptosis in an effector target-dependent manner. In addition, γδ T cells could induce autophagy of myeloma cells, inhibited the expression of autophagy-related PI3K, P-AKT and P-mTOR, while increased the expression of AMPK and Beclin-1.@*CONCLUSION@#γδ T cells can inhibit the proliferation of RPMI-8226 and U-266 myeloma cells, induce cell cycle arrest, promote apoptosis, and enhance autophagy in vitro. The mechanism may be related to inhibition of PI3K/AKT/mTOR signaling pathway and/or activation of AMPK/Beclin-1 signaling pathway.

A Case of Phagocytic Myeloma after Chemotherapy / 대한혈액학회지

Hemophagocytosis by myeloma cells after chemotherapy is a rare phenomenon. We have experienced a case of phagocytic, IgG, Kappa type plasma cell myeloma in a 41-year-old man after chemotherapy. Phagocytosis of erythrocytes and platelets was found.

Generation and Characterization of 1H8 monoclonal antibody against human bone marrow stromal cells

BACKGROUND: Bone marrow stromal cells (BMSCs) express many cell surface molecules, which regulate the proliferation and differentiation of immune cells within the bone marrow. METHODS: To identify cell surface molecules, which can regulate cell proliferation through cell interaction, monoclonal antibodies (MoAbs) against BMSCs were produced. Among them, 1H8 MoAb, which recognized distinctly an 80 kDa protein, abolished myeloma cell proliferation that was induced by co-culturing with BMSCs. RESULTS: IL-6 gene expression was increased when myeloma or stromal cells were treated with 1H8 MoAb. In addition, the expression of IL-6 receptor and CD40 was up-regulated by 1H8 treatment, suggesting that the molecule recognized by 1H8 MoAb is involved in cell proliferation by modulating the expression of cell growth-related genes. Myeloma cells contain high levels of reactive oxygen species (ROS), which are related to gene expression and tumorigenesis. Treatment with 1H8 decreased the intracellular ROS level and increased PAG antioxidant gene concomitantly. Finally, 1H8 induced the tyrosine phosphorylation of several proteins in U266. CONCLUSION: Taken together, 1H8 MoAb recognized the cell surface molecule and triggered the intracellular signals, which led to modulate gene expression and cell proliferation.

The effect of interleukin-2 (IL-2) synergized with IL-18 to enhance activities of natural killer cells / 西安交通大学学报(医学版)

Objective To explore potential synergetic effects of interleukin-2(IL-2) with IL-18 on induction of natural killer(NK) cell activity against myeloma cells in vitro.Methods CD69 expression on NK cells were defined by Flow Cytometry;IFN-? level in supernatants of NK cell culture was measured by ELISA;pure NK cell population was obtained from peripheral blood by using cell purification kit;standard Cr51 release method was used to test NK cell cytotoxicity against myeloma cells in vitro.Results The combined application of IL-18 with low dose of IL-2(10u/mL) significantly enhanced NK cell activation,IFN-? secretion and NK cell cytolytic activity against myeloma cells(U266 and RPMI-8226) as compared to IL-18 alone,respectively.Conclusion IL-2 synergized with IL-18 to induce NK cells activates anti-myeloma cell in vitro and combined use of IL-18 and low dose IL-2 could be an alterative immuno-therapy approach for cancers including myeloma.