Programmed cell death 1 (PD-1), CD127 and CD27/CD28 expression among CD8+ T cell subsets. were defined as naive [CD45RA+human leucocyte antigen D-related (HLA-DRC)], early effector (CD45RACHLA-DRC) and mature Treg (CD45RACHLA-DR+). Overall Treg frequency was increased significantly among CD3+CD4+ T cells in lenalidomide- (median = 167%) untreated (median = 81%) patients (= 741E-06). Among Treg mature cells were increased significantly in lenalidomide-treated patients (median = 282%) compared to untreated patients (median = 148%, = 0001) at the expense of naive Treg (lenalidomide median = 34%, untreated median = 118%, = 0003). (b) Absolute numbers of CD4+ T cells and Tregs including subsets in the indicated patient groups. Significant decrease of CD4+ T cells in lenalidomide-treated (median = 215/l) compared to untreated patients (median = 447/l, = 0006). Naive Treg Rabbit Polyclonal to MMP-11 were decreased (lenalidomide median = 110/l, untreated median = 492/l, = 0021) and mature Treg were increased (lenalidomide median = 122/l, untreated median = 45/l, = 0001). (c) Mature Treg frequencies during (-)-p-Bromotetramisole Oxalate lenalidomide therapy: lenalidomide induction or therapy stop in single patients. Boxes depict the interquartile range (IQR), the line the median and the whiskers the 95% confidence interval (CI). cei0177-0439-SD2.jpg (603K) GUID:?301BE568-67C4-4B1B-8D52-C8E1A7315894 Fig. S3. Influence of lenalidomide on natural killer (NK) cell frequency and activation status in multiple myeloma (MM) patients. (a) Box plots for NK cell frequency among all lymphocytes (left) and NKp46, NKp30 and NKG2D (right) represent untreated MM patients (= 36) and lenalidomide-treated patients (= 17). NKp46 [median mean fluorescence intensity (MFI) ut = 338, Lena = 486] and NKp30 (median MFI ut = 348, Lena = 553) were elevated significantly (NKp46: = 0028, NKp30: = 0029) on NK cells, whereas there was no difference in NKG2D expression (median MFI ut = 181, Lena = 180). Boxes depict the interquartile range (IQR), the line the median and the whiskers the 95% confidence interval (CI). (b) Correlation between NKp30 and NKp46 expression of NK cells was evaluated using the non-parametric Spearman’s rank test; Spearman’s correlation coefficient (are poorly defined. In an observational study we assessed the impact of lenalidomide on different populations of immune cells in multiple myeloma patients. Lenalidomide therapy was associated with increased amounts of a CD8+ T cell subset, phenotypically staged between classical central memory T cells (TCM) and effector memory T cells (TEM), consequently termed TCM/TEM. The moderate expression of perforin/granzyme and phenotypical profile of these cells identifies them as not yet terminally differentiated, which makes them promising candidates for the anti-tumour response. In addition, lenalidomide-treated patients showed higher abundance of CD14+ myeloid cells co-expressing CD15. This population was able to inhibit both CD4+ and CD8+ T cell proliferation and could thus be defined as a so far undescribed novel myeloid-derived suppressor cell (MDSC) subtype. We observed a striking correlation between levels of TCM/TEM, mature regulatory T cells (Tregs) and CD14+CD15+ MDSCs. (-)-p-Bromotetramisole Oxalate In summary, lenalidomide induces both activating and inhibitory components of the immune system, indicating the existence of potential counter-regulatory mechanisms. These findings provide new insights into the immunomodulatory action of lenalidomide. and [11]. (-)-p-Bromotetramisole Oxalate Reports on MDSC in human MM are scarce. To date, two publications report this cell type in (-)-p-Bromotetramisole Oxalate MM patients, one describing an increased frequency of human leucocyte antigen D-related (HLA-DR)lo monocytes in patients with MM at various stages of their disease [14] and the other observing granulocytic MDSCs in the peripheral blood and bone marrow of MM patients [15]. A promising approach to counteract immunoinhibitory effects in MM is the implementation of immunotherapeutic agents such as lenalidomide (CC-5013, IMiD3, Revlimid), which is an effective drug in the treatment of newly diagnosed and relapsed MM. Furthermore, it has been employed successfully for maintenance therapy after high-dose chemotherapy of MM patients [16]..