Multiple myeloma (MM) cells inhibit certain T-cell functions. We examined the expression of B7-H1 (PD-L1), a B7-related protein that inhibits T-cell responses, in CD138- IntroductionIn addition to the cytogenic and molecular abnormalities reportedly associated with malignant transformation of plasma cells, interactions between multiple myeloma (MM) cells and the bone marrow microenvironment are crucial for plasma cell survival and proliferation. [1][2][3] Several factors that mediate MM cell cross-talk with mesenchymalderived cells, such as vascular endothelial growth factor, an angiogenic factor, have been previously described; however, there is growing evidence that MM cells also interact with immune cells. Plasma cells interact with T cells via the RANK/RANK-L system. 4 A recent study demonstrated that the survival and growth of malignant plasma cells was supported by bone marrow dendritic cells via RANK/RANK-L and BAFF-APRIL. 5 There is also evidence that malignant plasma cells can be targeted for an immune response. Several tumor antigens are expressed by plasma cells isolated from MM and monoclonal gammopathy of undetermined significance (MGUS) patients, and allogenic bone marrow transplantation can induce a graft-versus-myeloma effect. [6][7][8] However, MM is also associated with immune dysfunction. Defects in T-cell responses to mitogenic and TCR-mediated stimulation have been reported. [9][10][11] Interestingly, regulatory T cell (T reg cell) populations are significantly modified in both MGUS and MM patients, suggesting that immune dysfunction is an early event in the malignant transformation process of plasma cells. 12,13 However, the factors produced by plasma cells that create these immune defects are poorly defined.A possible candidate responsible for such T-cell inhibitory mechanisms in MM plasma cells is B7-H1. B7-H1 (also known as PD-L1 or CD274) is a B7 family member and is the ligand for PD-1 (programmed death-1), a member of the CD28 family. 14 B7-H1 is broadly distributed in various tissues and cell types and is often expressed after exposure to inflammatory cytokines, especially IFN-␥. B7-H1 interacts with PD-1 and another as yet unknown receptor on T cells and can inhibit T cell activation and cytotoxic T lymphocytes (CTL)-mediated lysis. [15][16][17][18] B7-H1 can also increase T-cell activation. [19][20][21] Marked expression of B7-H1 has been reported for various human carcinomas and in mouse models expression of B7-H1 enhances tumor growth and allows dormant tumor cells to escape from CTLs. 16,[22][23][24][25][26][27][28][29] Blocking B7-H1 enhances the effects of cancer vaccines. [30][31][32][33][34] Toll-like receptor (TLR) stimulation can also induce B7-H1 expression in mouse tumor cells. 35 Thus, B7-H1 overexpression appears as a possible mechanism for tumors to avoid the host's immune response.Little is known regarding the expression of B7-H1 in B-lineage lymphocytes. We show here that B7-H1 is expressed by malignant plasma cells from most MM patients but not from MGUS patients. ...

clinicaltrials.gov identifier: NCT01437787.

No abstract

The addition of cladribine to the standard induction regimen is associated with increased rate of complete remission and improved survival of adult patients with AML.