scholarly journals Adhesion molecules on freshly recovered T leukemias promote tumor- directed lympholysis

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 138-143 ◽  
Author(s):  
CA Schirren ◽  
H Volpel ◽  
SC Meuer
Keyword(s):  
Tumor Cells ◽  
Adhesion Molecules ◽  
Leukemic Cells ◽  
Intercellular Adhesion Molecule ◽  
Cytotoxic Lymphocytes ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Human T Cell

Abstract Besides facilitating cell to cell adhesion, the molecular interactions between CD2 and its ligand CD58 (lymphocyte function-associated antigen- 3 [LFA-3]), as well as between CD11a/18 (LFA-1) and CD54 (intercellular adhesion molecule-1) have recently been recognized to participate in lymphocyte activation, recirculation, and effector function, including cytolytic activity towards tumor cells. We have investigated the role of CD2/CD58 and CD11a/18/CD54 interactions in cellular immune responses directed towards freshly recovered human T-cell leukemias. The data support the notion that downregulation of CD54 and CD58 correlates with enhanced numbers of blasts in circulation and unsusceptibility to killing by autologous cytotoxic lymphocytes. Importantly, after induction of CD54 and CD58 expression on leukemic cells by recombinant cytokines such as tumor necrosis factor-alpha, tumor cells become highly susceptible to lymphocyte-mediated lysis in vitro. Our findings, therefore, stress the point that successful immunotherapy of malignant disease may be facilitated by influencing not only the immune response itself, but also adhesion molecules on the malignant tumor targets.

scholarly journals Adhesion molecules on freshly recovered T leukemias promote tumor- directed lympholysis

Blood ◽  
1992 ◽  
Vol 79 (1) ◽  
pp. 138-143
Author(s):  
CA Schirren ◽  
H Volpel ◽  
SC Meuer
Keyword(s):  
Tumor Cells ◽  
Adhesion Molecules ◽  
Leukemic Cells ◽  
Intercellular Adhesion Molecule ◽  
Cytotoxic Lymphocytes ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Human T Cell

Besides facilitating cell to cell adhesion, the molecular interactions between CD2 and its ligand CD58 (lymphocyte function-associated antigen- 3 [LFA-3]), as well as between CD11a/18 (LFA-1) and CD54 (intercellular adhesion molecule-1) have recently been recognized to participate in lymphocyte activation, recirculation, and effector function, including cytolytic activity towards tumor cells. We have investigated the role of CD2/CD58 and CD11a/18/CD54 interactions in cellular immune responses directed towards freshly recovered human T-cell leukemias. The data support the notion that downregulation of CD54 and CD58 correlates with enhanced numbers of blasts in circulation and unsusceptibility to killing by autologous cytotoxic lymphocytes. Importantly, after induction of CD54 and CD58 expression on leukemic cells by recombinant cytokines such as tumor necrosis factor-alpha, tumor cells become highly susceptible to lymphocyte-mediated lysis in vitro. Our findings, therefore, stress the point that successful immunotherapy of malignant disease may be facilitated by influencing not only the immune response itself, but also adhesion molecules on the malignant tumor targets.

scholarly journals Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1)

2021 ◽  
Author(s):  
Nerea Allende-Vega ◽  
Joaquin Marco Brualla ◽  
Paolo Falvo ◽  
Catherine Alexia ◽  
Michael Constantinides ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Adhesion Molecule ◽  
Tumor Antigens ◽  
Intercellular Adhesion ◽  
Leukemic Cells ◽  
Intercellular Adhesion Molecule ◽  
Cytotoxic Lymphocytes ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Cytotoxic Lymphocyte

Abstract Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

scholarly journals Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1)

2021 ◽  
Author(s):  
Nerea Allende-Vega ◽  
Joaquin Marco Brualla ◽  
Paolo Falvo ◽  
Catherine Alexia ◽  
Michael Constantinides ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Adhesion Molecule ◽  
Tumor Antigens ◽  
Intercellular Adhesion ◽  
Leukemic Cells ◽  
Intercellular Adhesion Molecule ◽  
Cytotoxic Lymphocytes ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Cytotoxic Lymphocyte

Abstract Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

scholarly journals Metformin Sensitizes Leukemic Cells to Cytotoxic Lymphocytes by Increasing Expression of Intercellular Adhesion Molecule-1 (ICAM-1)

2021 ◽  
Author(s):  
Nerea Allende-Vega ◽  
Joaquin Marco Brualla ◽  
Paolo Falvo ◽  
Catherine Alexia ◽  
Michael Constantinides ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Adhesion Molecule ◽  
Tumor Antigens ◽  
Intercellular Adhesion ◽  
Leukemic Cells ◽  
Intercellular Adhesion Molecule ◽  
Cytotoxic Lymphocytes ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Cytotoxic Lymphocyte

Solid tumor cells have an altered metabolism that can protect them from cytotoxic lymphocytes. The antidiabetic drug metformin modifies tumor cell metabolism and several clinical trials are testing its effectiveness for the treatment of solid cancers. The use of metformin in hematologic cancers has received much less attention, although allogeneic cytotoxic lymphocytes are very effective against these tumors. We show here that metformin induces expression of Natural Killer G2-D (NKG2D) ligands (NKG2DL) and intercellular adhesion molecule-1 (ICAM-1), a ligand of the lymphocyte function-associated antigen 1 (LFA-1). This leads to enhance sensitivity to cytotoxic lymphocytes. Overexpression of antiapoptotic Bcl-2 family members decrease both metformin effects. The sensitization to activated cytotoxic lymphocytes is mainly mediated by the increase on ICAM-1 levels, which favors cytotoxic lymphocytes binding to tumor cells. Finally, metformin decreases the growth of human hematological tumor cells in xenograft models, mainly in presence of monoclonal antibodies that recognize tumor antigens. Our results suggest that metformin could improve cytotoxic lymphocyte-mediated therapy.

CD18 integrin and CD54-dependent neutrophil adhesion to cytokine-stimulated human hepatocytes

1997 ◽  
Vol 272 (3) ◽  
pp. G408-G416 ◽  
Author(s):  
A. R. Nagendra ◽  
J. K. Mickelson ◽  
C. W. Smith
Keyword(s):  
Cell Injury ◽  
Proteolytic Enzymes ◽  
Parenchymal Cell ◽  
Intercellular Adhesion Molecule ◽  
Human Neutrophils ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Necrosis Factor Alpha ◽  
Ifn Gamma

We investigated the hypothesis that CD54 (intercellular adhesion molecule-1) expressed on hepatocytes will support beta2-integrin (CD18)-dependent adhesion of neutrophils. An in vitro model using C3A cells (a human hepatoblastoma cell line exhibiting many characteristics of normal hepatocytes) and human neutrophils was utilized. C3A cells were stimulated with interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, or interferon-gamma (IFN-gamma) for 24 h to induce expression of CD54, and adhesion of neutrophils was found to be markedly increased. Detailed studies with IFN-gamma-stimulated (100 U/ml) C3A cells revealed that this adhesion involved CD11a/CD18 [lymphocyte function-associated antigen-1 (LFA-1)] and CD54 and was dependent on low levels of IL-8 produced by the stimulated hepatocytes. Addition of higher concentrations of chemotactic factor (e.g., IL-8) further augmented adhesion and recruited contributions of CD11b/CD18 (Mac-1). In contrast to LFA-1, Mac-1 appeared to recognize a CD54-independent ligand constitutively expressed on the hepatocytes. Such close apposition of neutrophils to hepatocytes may increase the potential for parenchymal cell injury by providing a short distance through which cytotoxic factors such as reactive oxygen or proteolytic enzymes could act.

RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia

Blood ◽  
2011 ◽  
Vol 118 (3) ◽  
pp. 638-649 ◽  
Author(s):  
Mark Holland ◽  
Fernanda V. Castro ◽  
Seema Alexander ◽  
Duncan Smith ◽  
Jizhong Liu ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
B Cell ◽  
Lymphoblastic Leukemia ◽  
Disease Onset ◽  
Flow Cytometric Analysis ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Cns Disease

Abstract We developed a murine model of CNS disease to obtain a better understanding of the pathogenesis of CNS involvement in pre-B-cell acute lymphoblastic leukemia (ALL). Semiquantitative proteomic discovery–based approaches identified unique expression of asparaginyl endopeptidase (AEP), intercellular adhesion molecule 1 (ICAM1), and ras-related C3 botulinum toxin substrate 2 (RAC2), among others, in an invasive pre-B-cell line that produced CNS leukemia in NOD-SCID mice. Targeting RAC2 significantly inhibited in vitro invasion and delayed disease onset in mice. Induced expression of RAC2 in cell lines with low/absent expression of AEP and ICAM1 did not result in an invasive phenotype or murine CNS disease. Flow cytometric analysis identified an enriched population of blast cells expressing ICAM1/lymphocyte function associated antigen-1 (LFA-1)/CD70 in the CD10+/CD19+ fraction of bone marrow aspirates obtained from relapsed compared with normal controls and those with primary disease. CD10+/CD19+ fractions obtained from relapsed patients also express RAC2 and give rise to CNS disease in mice. Our data suggest that combinations of processes are involved in the pathogenesis of CNS disease in pre-B-cell ALL, support a model in which CNS disease occurs as a result of external invasion, and suggest that targeting the processes of adhesion and invasion unique to pre-B cells may prevent recurrences within the CNS.

scholarly journals Absolute requirement of CD11/CD18 adhesion molecules, FcRII and the phosphatidylinositol-linked FcRIII for monoclonal antibody-mediated neutrophil antihuman tumor cytotoxicity

Blood ◽  
1992 ◽  
Vol 79 (6) ◽  
pp. 1484-1490 ◽  
Author(s):  
BH Kushner ◽  
NK Cheung
Keyword(s):  
Monoclonal Antibody ◽  
Adhesion Molecules ◽  
Leukocyte Adhesion ◽  
Neuroblastoma Cell ◽  
Intercellular Adhesion Molecule ◽  
Target Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Gm Csf

We have previously shown that 3F8, a murine IgG3, monoclonal antibody (MoAb) specific for the ganglioside GD2, mediates tumor cell kill in vitro and in vivo. We now describe receptor requirements of polymorphonuclear leukocytes (PMN) in 3F8-mediated cytotoxicity (ADCC) of human GD2 (+) melanoma and neuroblastoma cell lines. PMN from a child with leukocyte adhesion deficiency (LAD) were devoid of CD11/CD18 adhesion molecules and mounted no detectable ADCC. MoAb to CD11b, CD11c, and CD18 each efficiently blocked ADCC by normal PMN. In contrast, a panel of different MoAbs to CD11a had no significant inhibitory effect on ADCC, a finding consistent with the low-to-absent expression of the CD11a ligand, intercellular adhesion molecule-1, on the target cells. Granulocyte-macrophage colony-stimulating factor (GM- CSF) significantly increased the expression of CD11b, CD11c, and CD18 on normal PMN, decreased the expression of Fc receptors (FcR), and enhanced ADCC by normal but not by LAD PMN. MoAbs to FcRII and FcRIII each efficiently blocked ADCC; anti-FcRI MoAb had no effect. Flow cytometry using anti-FcRII MoAb versus anti-FcRIII MoAb did not show cross competition, suggesting that inhibition of ADCC was not a steric effect resulting from FcRII proximity to FcRIII. PMN deficient in FcRIII (obtained from patients with paroxysmal nocturnal hemoglobinuria) and PMN depleted of FcRIII by treatment with elastase or phosphatidylinositol (PI)-specific phospholipase C produced low ADCC, supporting a role for the PI-liked FcRIII. Thus, optimal ADCC using human PMN, human solid tumor cells, and a clinically active MoAb (conditions that contrast with the heterologous antibodies and nonhuman or nonneoplastic targets used in most models of PMN ADCC) required CD11b, CD11c, FcRII, and the PI-linked FcRIII. Furthermore, in this clinically relevant system, GM-CSF enhancement of antitumor PMN ADCC correlated with increased expression of CD11/CD18 molecules.

Adhesion Molecule LFA-1/ICAM-1 Influences on LPS-induced Megakaryocytic Emperipolesis in the Rat Bone Marrow

1997 ◽  
Vol 34 (5) ◽  
pp. 463-466 ◽  
Author(s):  
M. Tanaka ◽  
Y. Aze ◽  
T. Fujita
Keyword(s):  
Bone Marrow ◽  
Single Dose ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Flow Cytometric Analysis ◽  
Intercellular Adhesion Molecule ◽  
Lymphocyte Function ◽  
Intercellular Adhesion Molecule 1 ◽  
Flow Cytometric ◽  
Daily Dose

To investigate the effect of adhesion molecules on the occurrence of megakaryocytic emperipolesis of neutrophils, we examined the expression of lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1) in the bone marrow of lipopolysaccharide (LPS)-treated rats (experiment I) and the occurrence of megakaryocytic emperipolesis in anti-LFA-1 antibody-treated rats (experiment II). In experiment I, rats were injected with LPS intravenously at a daily dose of 0.5 mg/kg for 3 days. ICAM-1 was intensely stained on megakaryocytes in LPS-treated rats, as detected by flow cytometric analysis. ICAM-1 was immunostained in the megakaryocytes showing emperipolesis. LFA-1 was immunostained in the neutrophils engulfed by megakaryocytes. In experiment II, rats received anti-LFA-1 antibody intravenously at a single dose of 3 mg/kg. One hour after treatment, rats were given LPS intravenously at a single dose of 0.5 mg/kg. The incidence of megakaryocytic emperipolesis was markedly lower in the anti-LFA-1 antibody + LPS group than in the LPS alone group. These findings suggest that the occurrence of megakaryocytic emperipolesis is partly dependent on adhesion molecules via LFA-1/ICAM-1.

Endothelial adhesion molecules and their role in inflammation

1993 ◽  
Vol 71 (1) ◽  
pp. 76-87 ◽  
Author(s):  
C. Wayne Smith
Keyword(s):  
Endothelial Cells ◽  
Monoclonal Antibodies ◽  
Endothelial Cell ◽  
Cell Surface ◽  
Adhesion Molecules ◽  
Surrounding Tissue ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Endothelial Cell Surface

The emigration of leukocytes such as neutrophils into inflammatory sites requires adhesion to the endothelium of small venules. The initial adhesive event is margination characterized by rolling of neutrophils along the luminal surface of the endothelium. Each member of the selectin family of adhesion molecules has been shown to support neutrophil rolling under conditions of flow. E-selectin is synthesized by endothelial cells following cytokine stimulation, P-selectin is rapidly mobilized from Weibel–Palade bodies to the endothelial cell surface following stimulation with agents such as histamine, and L-selectin is constitutively expressed on the surface of leukocytes. Each selectin functions primarily as a lectin, recognizing carbohydrate structures on the leukocyte or endothelial cell surface. Once the marginated neutrophil forms a stationary adhesion with endothelial cells, it is stimulated by chemotactic factors to downregulate the selectin-based adhesion and upregulate adherence dependent on β2-integrins, principally CD11a/CD18 (LFA-1) and CD11b/CD18 (Mac-1). These adhesion molecules interact with intercellular adhesion molecule 1 (ICAM-1) and possibly other structures on the endothelial cell, and the leukocyte rapidly emigrates into surrounding tissue. Transendothelial migration in vitro is markedly inhibited by monoclonal antibodies against CD18 integrins or ICAM-1. Monoclonal antibodies against the selectins, CD18, CD11a, CD11b, and ICAM-1 have all been shown to significantly reduce the influx of neutrophils into sites of inflammation in various animal models.Key words: adhesion, integrins, selectins, leukocytes, endothelial cells.

scholarly journals Expression of adhesion molecules and chemotactic cytokines in cultured human mesothelial cells.

1992 ◽  
Vol 176 (4) ◽  
pp. 1165-1174 ◽  
Author(s):  
N Jonjić ◽  
G Peri ◽  
S Bernasconi ◽  
F L Sciacca ◽  
F Colotta ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Interleukin 1 ◽  
Mesothelial Cells ◽  
Mononuclear Phagocytes ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Ifn Gamma ◽  
Protein Levels

The mesothelium is a flat epithelial lining of serous cavities that could gate the traffic of molecules and cells between the circulation and these body compartments. The present study was designed to elucidate the capacity of mesothelial cells to express adhesion molecules and chemoattractant cytokines, two fundamental mechanisms of regulation of leukocyte recruitment. Cultured human mesothelial cells express appreciable levels of intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and these were increased by in vitro exposure to tumor necrosis factor (TNF), interferon gamma (IFN-gamma), or TNF and IFN-gamma. Interleukin 1 (IL-1) was a less consistent stimulus for adhesion molecule expression in vitro. Unlike endothelial cells, used as a reference cell population, resting or stimulated mesothelial cells did not express E-selectin and ICAM-2, as assessed by flow cytometry. Analysis of VCAM-1 mRNA by reverse transcriptase and polymerase chain reaction using appropriate primers revealed that mesothelial cells expressed both the seven- and the six-Ig domain transcripts, with predominance of the longer species. Monocytes bound appreciably to "resting" and, to a greater extent, to stimulated mesothelial cells. Monocytes exposed to IFN-gamma and lipopolysaccharide, used as prototypic activation signals, showed increased capacity to bind mesothelial cells. Anti-CD18 monoclonal antibody significantly inhibited binding of monocytes to mesothelial cells, and this blocking effect was amplified by anti-very late antigen 4. Mesothelial cells were able to express the chemotactic cytokines IL-8 and monocyte chemotactic protein 1 at the mRNA and protein levels. These results indicate that mesothelial cells can express a set of adhesion molecules (ICAM-1 and VCAM-1) overlapping with, but distinct from, that expressed in vascular endothelium (ICAM-1, ICAM-2, VCAM-1, E-selectin), and that these are functionally relevant for interacting with mononuclear phagocytes. The regulated expression of adhesion molecules and chemotactic cytokines by mesothelial cells is probably important in inflammatory and immune reactions that involve serous cavities, such as the long-known macrophage appearance and disappearance reactions.

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