Amplifying cancer vaccine responses by modifying pathogenic gene programs in tumor cells.


:Immunosuppressive factors, such as vascular endothelial growth factor, transforming growth factor-beta, prostaglandin E2, interleukin (IL)-10, and IL-6, are made frequently by cancer cells. These factors, along with others, can inhibit the development and function of tumor-reactive effector T cells and the clinical results of cancer vaccines. Production of these factors by tumor cells is associated with disease progression and may represent an active immune surveillance escape mechanism. However, a number of factors appear to be made directly in response to signaling molecules, such as RAS, AKT, and signal transducer and activator of transcription 3, which are activated as a result of genetic events that occur during oncogenesis. Methods to overcome the negative effects of immunosuppressive factors, which are "hard wired" into gene programs of cancer cells, might then improve the results of cancer vaccines. For example, specific blocking antibodies, which recognize such factors, or kinase inhibitors, which block the signaling pathways that lead to their production, could potentially be used as vaccine adjuvants. The effects of immunosuppressive factors may also be "turned off" by cytokines with tumor suppressor properties. The enhanced clinical and immunological effects of melanoma vaccines observed after the administration of high doses of interferon-alpha2b provide a "proof of principle" in human patients, that agents which counter the gene programs of cancer cells, causing them to intrinsically resist tumor-reactive T cells, may improve significantly the efficacy of cancer vaccines.


J Leukoc Biol


Spaner DE




Has Abstract


2004-08-01 00:00:00














  • Noncanonical dendritic cell differentiation and survival driven by a bacteremic pathogen.

    abstract::Maintenance of blood DC homeostasis is essential to preventing autoimmunity while controlling chronic infection. However, the ability of bacteremic pathogens to directly regulate blood DC homeostasis has not been defined. One such bacteremic pathogen, Porphyromonas gingivalis, is shown by our group to survive within m...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Miles B,Scisci E,Carrion J,Sabino GJ,Genco CA,Cutler CW

    更新日期:2013-08-01 00:00:00

  • Synthetic hexapeptides derived from the transmembrane envelope proteins of retroviruses suppress N-formylpeptide-induced monocyte polarization.

    abstract::Retroviral infections are frequently associated with immunosuppression. Retroviral transmembrane envelope proteins (TM proteins) play an important role in this phenomenon. CKS-17, a synthetic heptadecapeptide, represents the immunosuppressive site of these retroviral TM proteins. Here we support on the further delinea...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Oostendorp RA,Schaaper WM,Post J,Meloen RH,Scheper RJ

    更新日期:1992-03-01 00:00:00

  • IL-4 and IL-13 have overlapping but distinct effects on HIV production in monocytes.

    abstract::In HIV-1-infected monocytes and monocytoid cell lines, viral expression can be observed as high-level production, restricted (chronic low-level) expression, and latency (no viral expression). Interleukin-13 (IL-13) and IL-4, which have remarkedly similar deactivating effects on inflammatory monocyte functions, were st...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Mikovits JA,Meyers AM,Ortaldo JR,Minty A,Caput D,Ferrara P,Ruscetti FW

    更新日期:1994-09-01 00:00:00

  • ICAM-1: A master regulator of cellular responses in inflammation, injury resolution, and tumorigenesis.

    abstract::ICAM-1 is a cell surface glycoprotein and an adhesion receptor that is best known for regulating leukocyte recruitment from circulation to sites of inflammation. However, in addition to vascular endothelial cells, ICAM-1 expression is also robustly induced on epithelial and immune cells in response to inflammatory sti...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审


    authors: Bui TM,Wiesolek HL,Sumagin R

    更新日期:2020-09-01 00:00:00

  • Regulation of inflammation by cannabinoids, the endocannabinoids 2-arachidonoyl-glycerol and arachidonoyl-ethanolamide, and their metabolites.

    abstract::2-Arachidonoyl-glycerol (2-AG) and arachidonyl-ethanolamide (AEA) are endocannabinoids that have been implicated in many physiologic disorders, including obesity, metabolic syndromes, hepatic diseases, pain, neurologic disorders, and inflammation. Their immunomodulatory effects are numerous and are not always mediated...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审


    authors: Turcotte C,Chouinard F,Lefebvre JS,Flamand N

    更新日期:2015-06-01 00:00:00

  • It takes nerve to tell T and B cells what to do.

    abstract::The existence of an association between the brain and immunity has been documented. Data show that the nervous and immune systems communicate with one another to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity, which in turn, activates output through...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审


    authors: Kin NW,Sanders VM

    更新日期:2006-06-01 00:00:00

  • Dissociation between the translocation and the activation of Akt in fMLP-stimulated human neutrophils--effect of prostaglandin E2.

    abstract::PGE(2) and other cAMP-elevating agents are known to down-regulate most functions stimulated by fMLP in human polymorphonuclear neutrophils. We reported previously that the inhibitory potential of PGE(2) resides in its capacity to suppress fMLP-stimulated PI-3Kgamma activation via the PGE(2) receptor EP(2) and hence, t...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Burelout C,Naccache PH,Bourgoin SG

    更新日期:2007-06-01 00:00:00

  • The THC-induced suppression of Th1 polarization in response to Legionella pneumophila infection is not mediated by increases in corticosterone and PGE2.

    abstract::T helper cell type 1 (Th1)-polarizing cytokines are induced by Legionella pneumophila infection and are suppressed by pretreatment with marijuana cannabinoids (CB). Glucocorticoids and prostaglandin E2(PGE2) are also reported to suppress Th1 polarization and are induced by Delta9-tetrahydrocannabinol (THC), so their r...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Newton CA,Lu T,Nazian SJ,Perkins I,Friedman H,Klein TW

    更新日期:2004-10-01 00:00:00

  • Hepatitis C virus (HCV)-induced suppressor of cytokine signaling (SOCS) 3 regulates proinflammatory TNF-α responses.

    abstract::TNF-α is a proinflammatory cytokine, dramatically elevated during pathogenic infection and often responsible for inflammation-induced disease pathology. SOCS proteins are inhibitors of cytokine signaling and regulators of inflammation. In this study, we found that both SOCS1 and SOCS3 were transiently induced by TNF-α...

    journal_title:Journal of leukocyte biology

    pub_type: 临床试验,杂志文章


    authors: Collins AS,Ahmed S,Napoletano S,Schroeder M,Johnston JA,Hegarty JE,O'Farrelly C,Stevenson NJ

    更新日期:2014-08-01 00:00:00

  • Induction of granulysin in CD8+ T cells by IL-21 and IL-15 is suppressed by human immunodeficiency virus-1.

    abstract::Immunosuppression following infection with HIV-1 predisposes patients to a myriad of opportunistic pathogens, one of the most important of which is Mtb. Granulysin, expressed by NK cells and CTL, exhibits potent antimicrobial activity against Mtb and several other opportunistic pathogens associated with HIV-1 infectio...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Hogg AE,Bowick GC,Herzog NK,Cloyd MW,Endsley JJ

    更新日期:2009-11-01 00:00:00

  • Analysis of the synergistic stimulation of mouse macrophage proliferation by macrophage colony-stimulating factor (CSF-1) and tumor necrosis factor alpha (TNF-alpha).

    abstract::Tumor necrosis factor alpha (TNF-alpha) more than doubles tritiated thymidine ([3H]TdR) uptake in mouse macrophages stimulated by macrophage colony-stimulating factor (CSF-1). However, nothing is known of how TNF-alpha affects this increase or even whether it is manifested by increased cellular proliferation. Here we ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Guilbert LJ,Winkler-Lowen B,Smith A,Branch DR,Garcia-Lloret M

    更新日期:1993-07-01 00:00:00

  • Activation of EphA receptors on CD4+CD45RO+ memory cells stimulates migration.

    abstract::We have demonstrated previously that binding of ephrin-A1 to EphA receptors on human CD4(+) and CD8(+) T cells stimulates migration. Two EphA receptors have been reported in T cells: EphA1 at the protein level and EphA4 at the mRNA level. In this study, we wanted to investigate the expression profile of these receptor...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Holen HL,Nustad K,Aasheim HC

    更新日期:2010-06-01 00:00:00

  • Impaired NADPH oxidase activity in Rac2-deficient murine neutrophils does not result from defective translocation of p47phox and p67phox and can be rescued by exogenous arachidonic acid.

    abstract::Rac2 is a hematopoietic-specific Rho-GTPase that plays a stimulus-specific role in regulating reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and other functional responses in neutrophils. In this study, rac2-/- neutrophils were shown to have significantly decreased NADPH oxidase activit...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Kim C,Dinauer MC

    更新日期:2006-01-01 00:00:00

  • HLA-A2 down-regulation on primary human macrophages infected with an M-tropic EGFP-tagged HIV-1 reporter virus.

    abstract::Multiple mechanisms are used by the human immunodeficiency virus type 1 (HIV-1) to interfere with host-cell immune effector functions. The 27-kD Nef protein has been shown to down-modulate specific genes of the major histocompatibility complex class I (MHC-I) on the surface of infected primary T cells, facilitating th...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Brown A,Gartner S,Kawano T,Benoit N,Cheng-Mayer C

    更新日期:2005-09-01 00:00:00

  • CpG-B ODNs potently induce low levels of IFN-alphabeta and induce IFN-alphabeta-dependent MHC-I cross-presentation in DCs as effectively as CpG-A and CpG-C ODNs.

    abstract::Deoxycytidyl-deoxyguanosine [(CpG)3] oligodeoxynucleotides (ODNs) signal through TLR9 to induce type-I IFN (IFN-alphabeta) and IFN-alphabeta-dependent MHC-I cross-presentation of exogenous antigens by dendritic cells (DCs). A puzzle was presented by our observation that three ODN classes, CpG-A, CpG-B, and CpG-C, had ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Gray RC,Kuchtey J,Harding CV

    更新日期:2007-04-01 00:00:00

  • Effects of 8-aminoguanosine on the toxicity of guanosine and deoxyguanosine for malignant and normal lymphoid cells.

    abstract::The toxicity of guanosine and deoxyguanosine in the presence or absence of the purine nucleoside phosphorylase inhibitor, 8-aminoguanosine, for malignant lymphoid cell lines and mitogen-stimulated peripheral blood lymphocytes has been studied. Deoxyguanosine inhibited the proliferation of lymphoid cells more strongly ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: van der Kraan PM,van Zandvoort PM,De Abreu RA,Bakkeren JA

    更新日期:1988-07-01 00:00:00

  • Histone H4 directly stimulates neutrophil activation through membrane permeabilization.

    abstract::Extracellular histones have been implicated as a cause of tissue inflammatory injury in a variety of disorders including sepsis, lung, and liver diseases. However, little is known about their interactions with neutrophils and how this might contribute to injury. Here, it is shown that histone H4 acts as neutrophil act...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Hsieh IN,Deluna X,White MR,Hartshorn KL

    更新日期:2020-08-17 00:00:00

  • The monoclonal antibody MAC387 detects an epitope on the calcium-binding protein MRP14.

    abstract::The present study was initiated to identify the antigen recognized by the monoclonal antibody (MAb) MAC387 which is widely used for phenotypical characterization of myelomonocytic cells in situ. MAC387 has been described to show a similar reaction pattern as antisera to a complex formed by the calcium-binding proteins...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Goebeler M,Roth J,Teigelkamp S,Sorg C

    更新日期:1994-02-01 00:00:00

  • Combinatorial approach to cancer immunotherapy: strength in numbers.

    abstract::Immune-checkpoint blockade therapy with antibodies targeting CTLA-4 and PD-1 has revolutionized melanoma treatment by eliciting responses that can be remarkably durable and is now advancing to other malignancies. However, not all patients respond to immune-checkpoint inhibitors. Extensive preclinical evidence suggests...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审


    authors: Vilgelm AE,Johnson DB,Richmond A

    更新日期:2016-08-01 00:00:00

  • Protein kinase C agonists enhance phagocytosis of P. aeruginosa by murine alveolar macrophages.

    abstract::Pulmonary alveolar macrophages (AMphis) are incompetent to phagocytose unopsonized Pseudomonas aeruginosa, but ingestion by other macrophage phenotypes (i.e., peritoneal macrophages) occurs efficiently. The purpose of this study was to explore factors that might control such phenotypic differences. Our laboratory has ...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Heale JP,Speert DP

    更新日期:2001-01-01 00:00:00

  • IL-17 receptor signaling influences virus-induced corneal inflammation.

    abstract::IL-17 has been associated with selected inflammatory and autoimmune diseases. We characterized the expression of this proinflammatory cytokine following HSV-1 corneal infection and investigated whether IL-17R signaling modulated the host response to the viral pathogen at early time-points postinfection. IL-17 was elev...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Molesworth-Kenyon SJ,Yin R,Oakes JE,Lausch RN

    更新日期:2008-02-01 00:00:00

  • Modulation of neutrophil migration by exogenous gaseous nitric oxide.

    abstract::We studied the effect of exogenous nitric oxide (NO) on migration of rabbit peritoneal neutrophils. Exogenous NO enhanced random migration of neutrophils in a concentration-dependent way. An optimally stimulatory effect was observed with 0.5 microM NO, whereas at higher NO concentrations the enhancing effect decreased...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: VanUffelen BE,de Koster BM,Van den Broek PJ,VanSteveninck J,Elferink JG

    更新日期:1996-07-01 00:00:00

  • Plenary perspective: the complexity of constitutive and inducible gene expression in mononuclear phagocytes.

    abstract::Monocytes and macrophages differentiate from progenitor cells under the influence of colony-stimulating factors. Genome-scale data have enabled the identification of the set of genes that distinguishes macrophages from other cell types and the ways in which thousands of genes are regulated in response to pathogen chal...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章,评审


    authors: Hume DA

    更新日期:2012-09-01 00:00:00

  • Inhibition of neutrophil superoxide anion generation by platelet products: role of adenine nucleotides.

    abstract::Previously, we demonstrated the stimulus-specific ability of platelet lysate or release products to inhibit neutrophil functions in response to f-met-leu-phe (fMLP) or phorbol myristate acetate (PMA). The present study further characterizes these activities and identifies one of the platelet inhibitors of neutrophil s...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: McGarrity ST,Stephenson AH,Hyers TM,Webster RO

    更新日期:1988-11-01 00:00:00

  • Inhibition of glucocorticoid-mediated, caspase-independent dendritic cell death by CD40 activation.

    abstract::Glucocorticoids (GC) are potent anti-inflammatory and immunosuppressive agents that act on a variety of immune cells, including T cells, monocytes/macrophages, osteoclasts, and dendritic cells (DC). However, the mechanism(s) by which GC exert anti-inflammatory effects is still largely unknown. It is already well known...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Kim KD,Choe YK,Choe IS,Lim JS

    更新日期:2001-03-01 00:00:00

  • Epinephrine attenuates down-regulation of monocyte tumor necrosis factor receptors during human endotoxemia.

    abstract::Epinephrine inhibits lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) production by increasing intracellular cAMP concentrations. Because agents that increase cAMP levels can enhance TNF receptor expression in vitro, granulocyte and monocyte TNF receptors were determined by FACS-analysis in 7 normal humans...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: van der Poll T,Calvano SE,Kumar A,Coyle SM,Lowry SF

    更新日期:1997-02-01 00:00:00

  • A Cys-Gly-Cys triad in the dehydrogenase region of Nox2 plays a key role in the interaction with p67phox.

    abstract::p67(phox) is the paramount cytosolic regulator of the superoxide-generating Nox of phagocytes, by controlling the conformation of the catalytic component, Nox2. The initiating event of this process is a protein-protein interaction between p67(phox) and the part of Nox2 protruding into the cytosol, known as the dehydro...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Dahan I,Smith SM,Pick E

    更新日期:2015-11-01 00:00:00

  • No detectable NO synthesis from L-arginine or N(G)-hydroxy-L-arginine in fMLP-stimulated human blood neutrophils despite production of nitrite, nitrate, and citrulline from N(G)-hydroxy-L-arginine.

    abstract::Nitric oxide (NO) is a well-documented effector molecule in rodent phagocytes but its synthesis in human neutrophils has been controversial. In this study, NO production in human neutrophils activated by chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP) was measured in the presence of L-arginine (L-Ar...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Holm P,Kankaanranta H,Oja SS,Knowles RG,Moilanen E

    更新日期:1999-07-01 00:00:00

  • HIV-1 decreases Nrf2/ARE activity and phagocytic function in alveolar macrophages.

    abstract::Respiratory complications occur frequently in individuals living with human immunodeficiency-1 virus (HIV) infection, and there is evidence that HIV-related oxidative stress impairs alveolar macrophage immune function. We hypothesized that nuclear factor (erythroid-derived 2)-like 2 (Nrf2), a master transcription fact...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Staitieh BS,Ding L,Neveu WA,Spearman P,Guidot DM,Fan X

    更新日期:2017-08-01 00:00:00

  • Different patterns of deactivation of chemotaxis and haptotaxis of human peripheral blood mononuclear leukocytes by soluble and surface-bound attractants.

    abstract::Soluble mediators and inducible cell-surface and matrix-bound molecules coordinate the cascade of events giving rise to leukocyte emigration. Knowledge of the specific mechanisms underlying the attraction of cells into a local site, however, remains sketchy. In particular, it is unclear how chemoattractants cause rapi...

    journal_title:Journal of leukocyte biology

    pub_type: 杂志文章


    authors: Wiedermann CJ,Reinisch N,Bellmann R,Schratzberger P,Kowald E,Kähler CM

    更新日期:1995-10-01 00:00:00