Interactions of plasmacytoid dendritic cells with myeloma plasma cells and gamma/delta T cells in MGUS and multiple myeloma patients



Year of publication 2013
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Description Objectives: It is well accepted that the bone marrow microenvironment and the tumour-associated milieu of cell interactions plays a significant role in Multiple Myeloma (MM). However, the role of innate effector gamma/delta T cells in patients progressing from monoclonal gammopathy of undetermined significance (MGUS) to MM in this process is unknown. We have recently shown that Vdelta1 gamma/delta T lymphocytes isolated from myeloma patients exert specific cytotoxicity against primary CD38+CD138+ bone marrow derived plasma cells (Knight et al., Cytotherapy 2012). Large expansions of Vdelta1 gamma/delta T cells have been observed in MM patients suggesting their direct involvement in anti-myeloma immune responses. We hypothesized that the expansions of Vdelta1 gamma/delta T cells are driven by the cell interactions with plasmacytoid dendritic cells (pDC) within the bone marrow microenvironment. Methods: We have used fresh whole bone marrow (BM) and paired peripheral blood (PB) samples from MGUS (n=6) and newly diagnosed myeloma patients (n=21) to determine the frequencies of CD123+CD304+ pDC and Vdelta1 and Vdelta2 gamma/delta T cells by multicolour flow cytometry. Results: In MGUS patients, the median levels of Vdelta1 and Vdelta2 cells in the BM were 2.19 (range 0.55-8.05) and 0.63 (0.04-10.2) of CD3+ T cells respectively. Largely expanded levels of pDCs with CD45RA+HLA-DR+ phenotype were detected in MGUS patients in BM compared to healthy BM controls (n=4). In contrast, in newly diagnosed MM patients, the frequencies of pDCs were significantly reduced compared to MGUS patients (p<0.0001) or normal BM (p=0.0023). PB-derived pDC from MGUS or MM patients were numerically within the normal PB range (n=9). Conclusions: Our results show significantly elevated frequencies of Vdelta1 gammadelta T cell subset in patients progressing from MGUS to MM. In parallel, expanded levels of pDCs detected in the BM are believed to be driving the Vdelta1 gamma/delta T cell expansions. Further analyses of the key interactions between the target and effector cells through functional studies, gene expression profile and microarray analyses in patient cohorts will be discussed. Together, we provide evidence for the use of Vdelta1 gamma/delta T cells as a new mode of myeloma immunotherapy.
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