Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells

Vereecque, Rodolphe; Saudemont, Aurore; Quesnel, Bruno

doi:10.1038/sj.leu.2403391

Cited by 50 publications

(36 citation statements)

References 28 publications

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“…In addition, mouse leukemic cells exposed in vivo to Ara-C were more susceptible to CTL-mediated cell killing (Vereecque et al, 2004). This result suggests that the specific antileukemic activity of CTL, acting in synergy with enhanced sensitivity of leukemic cells to immune-mediated cell killing induced by chemotherapy, might eradicate minimal residual disease (van der Most et al, 2009).…”

Section: Discussionmentioning

confidence: 54%

“…The B7-CD28 signaling pathway is the most potent co-stimulatory pathway facilitating antigen-specific T-cell activation. An assay of human acute myelocytic leukemia cells demonstrated that exposure to doses of Ara-C as low as 0.05 mM led to a marked increase of CD86 and a lesser increase of CD80 (Vereecque et al, 2004). Most of specimens showed enhanced expression of CD80 or CD86, but some subtypes of acute myelocytic leukemia, especially FAB M0 and M1, showed no modification or a decrease of expression.…”

Section: Discussionmentioning

confidence: 99%

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Cytosine Arabinoside Promotes Cytotoxic Effect of T Cells on Leukemia Cells Mediated by Bispecific Antibody

Fan

Yang

et al. 2013

Human Gene Therapy

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Chemotherapeutic drugs can enhance an immune response of the host against the tumor in addition to killing cancer cells by direct cytotoxicity. Therefore, the combination of chemotherapy and immunotherapy is a promising approach for eliminating tumors, particularly in advanced stages. A strategic medication is to use a bispecific antibody format that is capable of recruiting polyclonal T cells around antibody-target-expressing tumor cells. Recently, we have constructed a bispecific antibody, anti-CD3 · anti-CD19, in a diabody configuration. In this study, we measured B7 family members B7.1 (CD80) and B7.2 (CD86) expressed on a CD19 + human leukemia cell line, Nalm-6, stimulated by cytosine arabinoside (Ara-C). We found that a low concentration of Ara-C could upregulate CD80 expressed on CD19 + Nalm-6 cells. The cytotoxicity of T lymphocytes against Nalm-6 cells in vitro and in vivo mediated by the anti-CD3 · anti-CD19 diabody with or without a low dose of Ara-C was compared. The combination of the anti-CD3 · anti-CD19 diabody and Ara-C showed the greatest effectiveness in enhancing the cytotoxicity of T cells against the tumor cells in vitro and in vivo. Activated T cells expressed higher levels of CD25 and CD69 and released more interleukin 2. Both perforin/granzyme B system and Fas/FasL pathway were involved in the diabody-induced T-cell cytotoxicity. Moreover, the activated T cells could upregulate ICAM-3 expression on Nalm-6 cells, and inhibition of LFA-1-ICAM-3 interaction impaired cytotoxicity of T cells. It was noted that Ara-C could upregulate CD80 expressed on two of five specimens of acute B lymphoblastic leukemia patient-derived cells. Cytotoxicity of T cells against these two patient-derived cells was enhanced in the presence of the anti-CD3 · anti-CD19 diabody. These findings indicate that treatment strategy using both cytotoxic lymphocyte-based immunotherapy and chemotherapy may have synergistic effects.

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Section: Discussionmentioning

confidence: 54%

Section: Discussionmentioning

confidence: 99%

Cytosine Arabinoside Promotes Cytotoxic Effect of T Cells on Leukemia Cells Mediated by Bispecific Antibody

Fan

Yang

et al. 2013

Human Gene Therapy

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“…Additional mechanisms aside from mAb blockade have also been investigated by several groups for modulating B7-H1 expression indirectly using IFN-g, CXCL10, and alternative methods. 76,80,85,113,114 Furthermore, combination therapy of B7-H1 blocking mAb along with a costimulatory CD137 mAb enhanced tumor regression. 72 In a recent model by Geng et al, 115 B7-H1 blockade with soluble PD-1 in combination with an HSP70 vaccine increased T H 1 cytokines and antitumor immunity in a murine lung metastasis model.…”

Section: Flies and Chenmentioning

confidence: 97%

The New B7s: Playing a Pivotal Role in Tumor Immunity

Flies

Chen

2007

Journal of Immunotherapy

179

136

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B7-H1, B7-DC, B7-H2, B7-H3, and B7-H4, all new additions to the B7 family, here termed "the new B7s," are emerging as important tools in directing immune function; each with unique, yet often overlapping functions. Clearly, each B7 molecule has developed its own indispensable niche in the immune system. The expression of both stimulatory and inhibitory B7 molecules seems to play an essential role in regulating the immune response to transformed cells through a variety of mechanisms. As specific niches of B7 family members continue to be dissected, their diagnostic and therapeutic potential becomes ever more apparent. In this review, we will discuss the role of the new B7s in activation and inhibition of antitumor immune responses, their prospects in diagnostics, and also potential and developing immunotherapy protocols.

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“…[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.…”

Section: Introductionmentioning

confidence: 99%

Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway

Liu

Hamrouni

Wolowiec

et al. 2007

Blood

551

446

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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. ...

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Cytosine arabinoside induces costimulatory molecule expression in acute myeloid leukemia cells

Cited by 50 publications

References 28 publications

Cytosine Arabinoside Promotes Cytotoxic Effect of T Cells on Leukemia Cells Mediated by Bispecific Antibody

Cytosine Arabinoside Promotes Cytotoxic Effect of T Cells on Leukemia Cells Mediated by Bispecific Antibody

The New B7s: Playing a Pivotal Role in Tumor Immunity

Plasma cells from multiple myeloma patients express B7-H1 (PD-L1) and increase expression after stimulation with IFN-γ and TLR ligands via a MyD88-, TRAF6-, and MEK-dependent pathway

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