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Idiotypic determinants are potential patient-specific tumor antigens in multiple myeloma (MM). In this study, we have determined the DNA sequence of the variable region of the tumor immunoglobulin (Ig) in 6 patients with MM. We then selected high affinity class I-restricted T-cell peptide epitopes in tumor Ig using two different internet-based epitope prediction programs. High affinity binding peptides were identified by at least one program in 4 out of 6 patients. Of these 35 peptides, only 3 scored high by both analyses. Given that all 6 patients had expanded T-cell clones with a cytotoxic (CD57[SUP+] CD8[SUP+] CD28[SUP-] perforin[SUP+]) phenotype, known to be associated with a longer survival and postulated to recognise tumor epitopes, this analysis indicates that such clones are unlikely to be exclusively directed towards tumor immuoglobulin, and suggests the need to expand the scope of the search for tumor epitopes with the ability to stimulate cytotoxic T cells in vivo. [ABSTRACT FROM AUTHOR]

Myeloid derived suppressor cells (MDSCs) are a heterogeneous population of cells that have been implicated as inhibitors of lymphopoiesis in patients with malignancies. They have a consensus phenotype of CD33+/CD11b+/HLA-DRlo/− and can be further divided into CD15 + granulocytic (G-MDSC) and CD14 + monocytic (M-MDSC) subsets. We characterized MDSCs in patients with multiple myeloma (MM) and found a significant increase in G-MDSCs in the blood of patients with progressive MM. Flow-sorted MDSCs from patients with MM induced the generation of regulatory T cells (Treg). MDSCs from both patients with MM and aged-matched controls demonstrated a dose-dependent inhibition of lymphocyte proliferation in carboxyfluorescein succinimidyl ester (CFSE)-tracking experiments. Granulocyte colony stimulating factor (G-CSF) administered to induce stem cell mobilization caused an increase in the number of MDSCs in the peripheral blood of patients with MM and a concentration of these immune-suppressive cells in peripheral blood stem cell collections. MDSCs are likely to cause immune dysfunction in patients with MM. [ABSTRACT FROM AUTHOR]

Discrepancies in the literature between regulatory T cell (Treg) and pro-inflammatory T helper 17 (Th17) numbers in multiple myeloma (MM) can be largely explained by technical differences in methodology and patient selection. In this study, Treg cells were defined as CD3+CD4+CD25++CD127lo cells. Patients with MM ( n = 20) had a significant imbalance in Treg/Th17 ratio when compared with either aged-matched controls ( n = 28) or other monoclonal gammopathies, and this was associated with a significantly worse survival. The percent Treg in bone marrow of patients with MM was higher than that in matched peripheral blood samples ( p = 0.02), although FOXP3 expression within bone marrow T cells was lower ( p = 0.02). We observed increased Treg function, both in vivo and in vitro, due at least partially to an increase in CTLA-4 expression by concurrent treatment with dexamethasone and immune modulatory compounds (iMiDs). We suggest that immunoregulatory balance is important during active chemotherapy and that conclusions related to the immunostimulatory effect of iMiDs based on in vitro testing must be considered with caution. [ABSTRACT FROM AUTHOR]

The expanded T cell clones are associated with a prolonged survival in patients with multiple myeloma. We sought to confirm this prognostic significance in a multicenter patient cohort and investigate the effect of thalidomide on clones and T regulatory cells (Tregs). Blood was collected from 120 patients enrolled in a Phase III trial of maintenance therapy ± thalidomide after autologous stem cell transplantation. TCR Vβ repertoire analysis identified T cell expansions in 48% of patients pre-transplant and 68% after 8-month maintenance. T cell expansions, previously shown to be clonal, were predominantly CD8 + (93%) and all 24 TCR Vβ families tested were represented. Thalidomide therapy was associated with a significant increase in the incidence of patients with multiple expansions (49% vs. 23%; χ2=6.8; p=0.01). The presence of expansions regardless of therapy was associated with a significantly longer median progression free survival (PFS) (32.1 vs. 17.6 months; χ2=5.6; p=0.02) and overall survival (OS) (χ2=3.9; p<0.05). Median PFS in the thalidomide arm was 50.9 months for patients with expansions and 28.3 months for patients without expansions (χ2=19.4; p=0.0002). Thalidomide did not appear to modulate Treg numbers. Expanded T cell clones are prognostically significant and have an impact on progression after thalidomide therapy in a proportion of patients. [ABSTRACT FROM AUTHOR]

The article presents a study on the use of an evidence of up-regulated fibroblast growth factor receptor 3 (FGFR3) to detect measurable residual disease (MRD) in both bone marrow (BM) and peripheral blood (PB) samples from patients with multiple myeloma (MM). The gene expression data showed that most patients with MM would have either unregulated FGFR3, cyclin D3 or c-maf expression. The study shows that dPCR possesses sufficient sensitivity for the detection of MRD in MM patients.

A letter to the editor is presented in response to the article about the presence of side population (SP) cells in multuple myeloma.