Analysis of gamma-delta T cells and plasmacytoid dendriticcells in MGUS and Multiple Myeloma patients

Multiple Myeloma (MM) remains incurable B-cell malignancy despite novel therapies. Plasmacytoid dendritic cells (pDC) have been shown to mediate tumour plasma cell growth, survival and drug resistance in MM patients. The role of effector gammadelta T cell interactions with pDC in patients progressing from monoclonal gammopathy of undetermined significance (MGUS) to MM is unknown. Our aim was to determine frequencies and phenotypes of pDC together with Vdelta1 and Vdelta2 gammadelta T cells. We used bone marrow (BM) and paired peripheral blood (PB) samples from MGUS (n=8) and newly diagnosed myeloma (n=11) patients. Total of n=24 age-matched healthy donors samples have been analysed. PDCs were analysed by multicolour flow cytometry as CD123+, CD303+, and CD304+. Phenotype of active pDC was identified as HLA-DR+ CD45RA+. In MGUS and MM patients, the medians of Vdelta1 T cells were comparable to normal levels in contrast to Vdelta2 T cells being significantly decreased in both patient cohorts. In newly diagnosed MM patients, frequencies of pDCs were shown significantly reduced compared to MGUS patients (p=0.012) or normal BM (p<0.0001). PB-derived pDC from patient cohorts were numerically within the normal range. All normal pDC samples presented an active phenotype in contrast to only 50% of MGUS or MM patients. In summary, we found dramatic differences in gammadelta T cells and pDC numbers and phenotype in BM of myeloma patients. Further analyses of the key interactions between the pDC, myeloma and gammadelta T cells through functional studies, gene expression profiles in patient cohorts will be discussed.