Compartment-Specific Bioluminescence Imaging platform for the high-throughput evaluation of antitumor immune function.

Abstract:

:Conventional assays evaluating antitumor activity of immune effector cells have limitations that preclude their high-throughput application. We adapted the recently developed Compartment-Specific Bioluminescence Imaging (CS-BLI) technique to perform high-throughput quantification of innate antitumor activity and to show how pharmacologic agents (eg, lenalidomide, pomalidomide, bortezomib, and dexamethasone) and autologous BM stromal cells modulate that activity. CS-BLI-based screening allowed us to identify agents that enhance or inhibit innate antitumor cytotoxicity. Specifically, we identified compounds that stimulate immune effector cells against some tumor targets but suppressed their activity against other tumor cells. CS-BLI offers rapid, simplified, and specific evaluation of multiple conditions, including drug treatments and/or cocultures with stromal cells and highlights that immunomodulatory pharmacologic responses can be heterogeneous across different types of tumor cells. This study provides a framework to identify novel immunomodulatory agents and to prioritize compounds for clinical development on the basis of their effect on antitumor immunity.

journal_name

Blood

journal_title

Blood

authors

McMillin DW,Delmore J,Negri JM,Vanneman M,Koyama S,Schlossman RL,Munshi NC,Laubach J,Richardson PG,Dranoff G,Anderson KC,Mitsiades CS

doi

10.1182/blood-2011-04-348490

subject

Has Abstract

pub_date

2012-04-12 00:00:00

pages

e131-8

issue

15

eissn

0006-4971

issn

1528-0020

pii

blood-2011-04-348490

journal_volume

119

pub_type

杂志文章

相关文献

BLOOD文献大全
  • Mitochondrial clearance is regulated by Atg7-dependent and -independent mechanisms during reticulocyte maturation.

    abstract::Mitochondrial clearance is a well recognized but poorly understood biologic process, and reticulocytes, which undergo programmed mitochondrial clearance, provide a useful model to study this phenomenon. At the ultrastructural level, mitochondrial clearance resembles an autophagy-related process; however, the role of a...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-04-151639

    authors: Zhang J,Randall MS,Loyd MR,Dorsey FC,Kundu M,Cleveland JL,Ney PA

    更新日期:2009-07-02 00:00:00

  • Genistein reduces tumor necrosis factor alpha-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells.

    abstract::The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PA...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: van Hinsbergh VW,Vermeer M,Koolwijk P,Grimbergen J,Kooistra T

    更新日期:1994-11-01 00:00:00

  • The mechanism of tumor cell clearance by rituximab in vivo in patients with B-cell chronic lymphocytic leukemia: evidence of caspase activation and apoptosis induction.

    abstract::Rituximab is a chimeric monoclonal antibody directed at CD20 with significant activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). A variety of pathways of tumor cytotoxicity different from cytotoxic chemotherapy have been proposed for this therapeutic antibody including antibody-dependent ce...

    journal_title:Blood

    pub_type: 临床试验,杂志文章,多中心研究

    doi:10.1182/blood.v99.3.1038

    authors: Byrd JC,Kitada S,Flinn IW,Aron JL,Pearson M,Lucas D,Reed JC

    更新日期:2002-02-01 00:00:00

  • Participation of the urokinase receptor in neutrophil efferocytosis.

    abstract::The urokinase receptor (uPAR) plays an important role in regulation of fibronolysis, cell migration, and adhesion. In this study, we examined whether uPAR plays a role in modulating efferocytosis of neutrophils. Macrophages from uPAR(-/-) mice demonstrated enhanced ability to engulf viable wild-type (WT) neutrophils i...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-12-193524

    authors: Park YJ,Liu G,Tsuruta Y,Lorne E,Abraham E

    更新日期:2009-07-23 00:00:00

  • Aberrant DNA methylation and epigenetic inactivation of Eph receptor tyrosine kinases and ephrin ligands in acute lymphoblastic leukemia.

    abstract::Eph receptors and their ephrin ligands are involved in normal hematopoietic development and tumorigenesis. Using methylated CpG island amplification/DNA promoter microarray, we identified several EPH receptor and EPHRIN genes as potential hypermethylation targets in acute lymphoblastic leukemia (ALL). We subsequently ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2009-05-222208

    authors: Kuang SQ,Bai H,Fang ZH,Lopez G,Yang H,Tong W,Wang ZZ,Garcia-Manero G

    更新日期:2010-03-25 00:00:00

  • Human CD8+CD25+ thymocytes share phenotypic and functional features with CD4+CD25+ regulatory thymocytes.

    abstract::CD8+CD25+ cells, which expressed high levels of Foxp3, glucocorticoid-induced tumor necrosis factor receptor (GITR), CCR8, tumor necrosis factor receptor 2 (TNFR2), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) mRNAs, were identified in the fibrous septa and medullary areas of human thymus. Activated CD8+CD...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2003-04-1320

    authors: Cosmi L,Liotta F,Lazzeri E,Francalanci M,Angeli R,Mazzinghi B,Santarlasci V,Manetti R,Vanini V,Romagnani P,Maggi E,Romagnani S,Annunziato F

    更新日期:2003-12-01 00:00:00

  • Oxidation-induced changes in microrheologic properties of the red blood cell membrane.

    abstract::It has been hypothesized that some of the irreversible microrheologic abnormalities of sickle red blood cell (RBC) membranes could result from autoxidative perturbation. To model this possibility, we used micromechanical manipulation to examine the static extensional rigidity and inelastic or plastic behavior of norma...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hebbel RP,Leung A,Mohandas N

    更新日期:1990-09-01 00:00:00

  • The inhibitory anti-FGFR3 antibody, PRO-001, is cytotoxic to t(4;14) multiple myeloma cells.

    abstract::The association of fibroblast growth factor receptor 3 (FGFR3) expression with t(4;14) multiple myeloma (MM) and the demonstration of the transforming potential of this receptor tyrosine kinase (RTK) make it a particularly attractive target for drug development. We report here a novel and highly specific anti-FGFR3-ne...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2005-10-4179

    authors: Trudel S,Stewart AK,Rom E,Wei E,Li ZH,Kotzer S,Chumakov I,Singer Y,Chang H,Liang SB,Yayon A

    更新日期:2006-05-15 00:00:00

  • Cabbage seed protease inhibitor: a slow, tight-binding inhibitor of trypsin with activity toward thrombin, activated Stuart factor (factor Xa), activated Hageman factor (factor XIIa), and plasmin.

    abstract::An inhibitor of procoagulant and fibrinolytic enzymes was derived from cabbage seeds by a procedure using acetone precipitation, ion-exchange chromatography, and gel filtration. The cabbage seed inhibitor was a 10-Kd monomeric protein with intrachain disulfide bonds. This preparation prevented clot formation in whole ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Carter TH,Everson BA,Ratnoff OD

    更新日期:1990-01-01 00:00:00

  • CCAAT/Enhancer binding proteins repress the leukemic phenotype of acute myeloid leukemia.

    abstract::CCAAT/enhancer binding proteins (C/EBPs) are a family of factors that regulate cell growth and differentiation. These factors, particularly C/EBPalpha and C/EBPepsilon, have important roles in normal myelopoiesis. In addition, loss of C/EBP activity appears to have a role in the pathogenesis of myeloid disorders inclu...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2002-05-1374

    authors: Truong BT,Lee YJ,Lodie TA,Park DJ,Perrotti D,Watanabe N,Koeffler HP,Nakajima H,Tenen DG,Kogan SC

    更新日期:2003-02-01 00:00:00

  • Epinephrine-induced activation of LW-mediated sickle cell adhesion and vaso-occlusion in vivo.

    abstract::Sickle red cell (SS RBC) adhesion is believed to contribute to the process of vaso-occlusion in sickle cell disease (SCD). We previously found that the LW RBC adhesion receptor can be activated by epinephrine to mediate SS RBC adhesion to endothelial alphavbeta3 integrin. To determine the contribution of LW activation...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2006-11-056101

    authors: Zennadi R,Moeller BJ,Whalen EJ,Batchvarova M,Xu K,Shan S,Delahunty M,Dewhirst MW,Telen MJ

    更新日期:2007-10-01 00:00:00

  • Stomatin, flotillin-1, and flotillin-2 are major integral proteins of erythrocyte lipid rafts.

    abstract::Lipid rafts are sphingolipid- and cholesterol-rich membrane microdomains that are insoluble in nonionic detergents, have a low buoyant density, and preferentially contain lipid-modified proteins, like glycosyl phosphatidylinositol (GPI)-anchored proteins. The lipid rafts were isolated from human erythrocytes and major...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.4.1141

    authors: Salzer U,Prohaska R

    更新日期:2001-02-15 00:00:00

  • FLT3/FLK2 ligand promotes the growth of murine stem cells and the expansion of colony-forming cells and spleen colony-forming units.

    abstract::The effect of FLT3/FLK2 ligand (FL) on the growth of primitive hematopoietic cells was investigated using ThyloSca1+ stem cells. FL was observed to interact with a variety of factors to initiate colony formation by stem cells. When stem cells were stimulated in liquid culture with FL plus interleukin (IL)-3, IL-6, gra...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Hudak S,Hunte B,Culpepper J,Menon S,Hannum C,Thompson-Snipes L,Rennick D

    更新日期:1995-05-15 00:00:00

  • Increased calcium permeability of cold-stored erythrocytes.

    abstract::The calcium, sodium, and magnesium permeability of erythrocytes from blood stored at 4 degrees C in various anticoagulant media has been studied and compared to that of fresh erythrocytes. Passive influx of CA2+ was measured at 37 degrees C in cells pretreated to abolish Ca2+ pumping and was up to fivefold greater for...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Wiley JS,McCulloch KE,Bowden DS

    更新日期:1982-07-01 00:00:00

  • Notes from the Director, National Heart, Lung, and Blood Institute: transitions.

    abstract::During this time of transition in the federal government and the National Institutes of Health, I write to assure the Blood community of the National Heart, Lung, and Blood Institute's (NHLBI) commitment to new and established investigators as outlined in the NHLBI Strategic Plan. This perspective discusses the NHLBI ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2008-12-194100

    authors: Nabel EG

    更新日期:2009-03-26 00:00:00

  • Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis.

    abstract::We studied the impact of driver mutations of JAK2, CALR, (calreticulin gene) or MPL on clinical course, leukemic transformation, and survival of patients with primary myelofibrosis (PMF). Of the 617 subjects studied, 399 (64.7%) carried JAK2 (V617F), 140 (22.7%) had a CALR exon 9 indel, 25 (4.0%) carried an MPL (W515)...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2014-05-578435

    authors: Rumi E,Pietra D,Pascutto C,Guglielmelli P,Martínez-Trillos A,Casetti I,Colomer D,Pieri L,Pratcorona M,Rotunno G,Sant'Antonio E,Bellini M,Cavalloni C,Mannarelli C,Milanesi C,Boveri E,Ferretti V,Astori C,Rosti V,Cerva

    更新日期:2014-08-14 00:00:00

  • alpha2beta1 integrin expression in the tumor microenvironment enhances tumor angiogenesis in a tumor cell-specific manner.

    abstract::To define the role of the alpha2beta1 integrin in pathologic angiogenesis, we investigated tumor-associated growth and angiogenesis in wild-type and alpha2-null mice. Our findings reveal that the alpha2beta1 integrin plays an important role in angiogenesis via regulation of VEGFR1 expression. When challenged with B16F...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2007-06-094680

    authors: Zhang Z,Ramirez NE,Yankeelov TE,Li Z,Ford LE,Qi Y,Pozzi A,Zutter MM

    更新日期:2008-02-15 00:00:00

  • Lentivirus-transduced human monocyte-derived dendritic cells efficiently stimulate antigen-specific cytotoxic T lymphocytes.

    abstract::Dendritic cells (DCs) are professional antigen-presenting cells that are highly effective adjuvants for immunizing against pathogens and tumor antigens. The potential merit of genetic approaches to loading DCs with antigens is to express high and sustained levels of proteins that can be subsequently processed and pres...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.1.114

    authors: Dyall J,Latouche JB,Schnell S,Sadelain M

    更新日期:2001-01-01 00:00:00

  • Antibody-mediated marrow failure after allogeneic bone marrow transplantation.

    abstract::Marrow graft failure observed in association with histocompatibility differences between donor and recipient is often attributed to rejection mediated by host-derived cytolytic T lymphocytes. The data presented in this report indicate that persistent host antibodies specific for donor antigen may also mediate graft fa...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Barge AJ,Johnson G,Witherspoon R,Torok-Storb B

    更新日期:1989-10-01 00:00:00

  • Increased basal and induced tyrosine phosphorylation of the insulin-like growth factor I receptor beta subunit in circulating mononuclear cells of patients with polycythemia vera.

    abstract::We have previously shown that circulating progenitor cells in patients with polycythemia vera (PV) are hypersensitive to insulin-like growth factor I (IGF-I) with respect to erythroid burst formation in serum-free medium, and that this effect occurs through the IGF-I receptor. To investigate the molecular basis of thi...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Mirza AM,Correa PN,Axelrad AA

    更新日期:1995-08-01 00:00:00

  • T-cell depletion of bone marrow transplants for leukemia from donors other than HLA-identical siblings: advantage of T-cell antibodies with narrow specificities.

    abstract::T-cell depletion of donor marrow decreases graft-versus-host disease resulting from transplants from unrelated and human leukocyte antigen (HLA)-mismatched related donors. However, there are diverse strategies for T-cell-depleted transplantation, and it is uncertain whether any improve leukemia-free survival (LFS). To...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Champlin RE,Passweg JR,Zhang MJ,Rowlings PA,Pelz CJ,Atkinson KA,Barrett AJ,Cahn JY,Drobyski WR,Gale RP,Goldman JM,Gratwohl A,Gordon-Smith EC,Henslee-Downey PJ,Herzig RH,Klein JP,Marmont AM,O'Reilly RJ,Ringdén O,Slav

    更新日期:2000-06-15 00:00:00

  • Targeted inhibition of calcineurin signaling blocks calcium-dependent reactivation of Kaposi sarcoma-associated herpesvirus.

    abstract::Kaposi sarcoma-associated herpesvirus (KSHV) is associated with KS, primary effusion lymphoma (PEL), and multicentric Castleman disease. Reactivation of KSHV in latently infected cells and subsequent plasma viremia occur before the development of KS. Intracellular signaling pathways involved in KSHV reactivation were ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood.v97.8.2374

    authors: Zoeteweij JP,Moses AV,Rinderknecht AS,Davis DA,Overwijk WW,Yarchoan R,Orenstein JM,Blauvelt A

    更新日期:2001-04-15 00:00:00

  • The reliability and specificity of c-kit for the diagnosis of acute myeloid leukemias and undifferentiated leukemias. The European Group for the Immunological Classification of Leukemias (EGIL).

    abstract::We document findings on c-kit (CD117) expression in 1,937 pediatric and adult de novo acute leukemia cases, diagnosed in five single European centers. All cases were well characterized as to the morphologic, cytochemical, and immunologic features, according to the European Group for the Immunological Classification of...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Bene MC,Bernier M,Casasnovas RO,Castoldi G,Knapp W,Lanza F,Ludwig WD,Matutes E,Orfao A,Sperling C,van't Veer MB

    更新日期:1998-07-15 00:00:00

  • Definitive but not primitive hematopoiesis is impaired in jumonji mutant mice.

    abstract::A novel gene, jumonji was identified by a mouse gene trap strategy. The jumonji gene encodes a protein containing a putative DNA binding domain. The mice homozygous for jumonji gene with a BALB/cA genetic background show hypoplasia of the fetal liver and embryonic lethality, suggesting impaired hematopoiesis. In the p...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Kitajima K,Kojima M,Nakajima K,Kondo S,Hara T,Miyajima A,Takeuchi T

    更新日期:1999-01-01 00:00:00

  • Large granular lymphocyte proliferation: an analysis of T-cell receptor gene arrangement and expression and the effect of in vitro culture with inducing agents.

    abstract::The status of the T cell receptor beta and gamma genes in natural killer (NK) cells was investigated in two patients with a marked expansion of CD2+, CD3- NK cells. Both genes were found to be in the germline state. The T alpha and complete T beta gene transcripts were not detected, but a 1.0-kilobase T beta gene tran...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Chan WC,Dahl C,Waldmann T,Link S,Mawle A,Nicholson J,Bach FH,Bongiovanni K,McCue PA,Winton EF

    更新日期:1988-01-01 00:00:00

  • (Dicer)phering roles of microRNA in platelets.

    abstract::In this issue of Blood, Rowley et al report that noncoding RNAs precisely regulate the messenger RNA (mRNA) profile in platelets. Interfering in this process using genetically engineered mice affects hemostatic and thrombotic functions of platelets. ...

    journal_title:Blood

    pub_type: 评论,杂志文章

    doi:10.1182/blood-2016-01-694893

    authors: Boilard E,Belleannée C

    更新日期:2016-04-07 00:00:00

  • B cells in early and chronic HIV infection: evidence for preservation of immune function associated with early initiation of antiretroviral therapy.

    abstract::Characterization of lymphocytes including B cells during early versus chronic HIV infection is important for understanding the impact of chronic viremia on immune cell function. In this setting, we investigated B cells before and after reduction of HIV plasma viremia by antiretroviral therapy (ART). At baseline, perip...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2010-05-285528

    authors: Moir S,Buckner CM,Ho J,Wang W,Chen J,Waldner AJ,Posada JG,Kardava L,O'Shea MA,Kottilil S,Chun TW,Proschan MA,Fauci AS

    更新日期:2010-12-16 00:00:00

  • Deficient lipoxin synthesis: a novel platelet dysfunction in myeloproliferative disorders with special reference to blastic crisis of chronic myelogenous leukemia.

    abstract::The capacity to convert exogenous leukotriene A4 to lipoxins (LXs) was investigated in platelet suspensions from patients with myeloproliferative disorders (MPD) (n = 22) and healthy control subjects (n = 14). Platelets isolated from the controls produced mainly LXA4, but also 6(S)-LXA4 and the all-trans isomers of li...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Stenke L,Edenius C,Samuelsson J,Lindgren JA

    更新日期:1991-12-01 00:00:00

  • Molecular determinants of clinical expression of hereditary elliptocytosis and pyropoikilocytosis.

    abstract::The clinical severity of common hereditary elliptocytosis (HE) is highly variable, ranging from an asymptomatic carrier state to a severe hemolytic anemia. To elucidate the molecular basis of this variable clinical expression, we evaluated 56 subjects from 24 HE kindred, who carry alpha spectrin mutants characterized ...

    journal_title:Blood

    pub_type: 杂志文章

    doi:

    authors: Coetzer T,Lawler J,Prchal JT,Palek J

    更新日期:1987-09-01 00:00:00

  • Analysis of the clonal growth and differentiation dynamics of primitive barcoded human cord blood cells in NSG mice.

    abstract::Human cord blood (CB) offers an attractive source of cells for clinical transplants because of its rich content of cells with sustained repopulating ability in spite of an apparent deficiency of cells with rapid reconstituting ability. Nevertheless, the clonal dynamics of nonlimiting CB transplants remain poorly under...

    journal_title:Blood

    pub_type: 杂志文章

    doi:10.1182/blood-2013-06-508432

    authors: Cheung AM,Nguyen LV,Carles A,Beer P,Miller PH,Knapp DJ,Dhillon K,Hirst M,Eaves CJ

    更新日期:2013-10-31 00:00:00