Abstract:
:One of the major limitations for cancer immunotherapy is related to the frequent existence of an intra-tumoral immunosuppressive environment, to which STAT3 (Signal transducer and activator of transcription-3) activation in tumor and dendritic cells (DCs) are believed to contribute. In this study, we tested the hypothesis that the combination of CpG (a DC activator) and JSI-124 (a STAT3 inhibitor) may generate synergistic antitumor effects compared to CpG or JSI-124 alone. B16-F10, a mouse melanoma cell line that has constitutively active STAT3, was grafted in C57BL/6 mice and then tumor-bearing mice treated intra-tumorally with (a) phosphate buffered saline, (b) 10 microg CpG, (c) 1 mg kg(-1) JSI-124 or (d) 10 microg CpG+1 mg kg(-1) JSI-124. The effects of treatments on tumor growth, survival and antitumor immune responses were evaluated. Although significant antitumor effects were detected with the single-agent treatments, the CpG+JSI-124 treatment resulted in synergistic antitumor effects compared to CpG or JSI-124 alone. Correlating with these findings, the combination therapy resulted in significantly higher intra-tumoral levels of several proinflammatory, TH1-related cytokines (including IL-12, IFN-gamma, TNF-alpha and IL-2), increases in intra-tumoral CD8+ and CD4+ T cells expressing activation/memory markers and NK cells and increases in activated DCs in the tumors and regional lymph nodes (LNs). Concomitantly, the combination therapy led to a significantly decreased level of immunosuppression, as evidenced by lower intra-tumoral level of VEGF and TGF-beta, and decreased number of CD4+CD25+Foxp3+ regulatory T cells in the regional LNs. This study has provided the proof-of-principle for combining CpG and JSI-124 to enhance antitumor immune responses.
journal_name
Immunol Cell Bioljournal_title
Immunology and cell biologyauthors
Molavi O,Ma Z,Hamdy S,Lai R,Lavasanifar A,Samuel Jdoi
10.1038/icb.2008.27subject
Has Abstractpub_date
2008-08-01 00:00:00pages
506-14issue
6eissn
0818-9641issn
1440-1711pii
icb200827journal_volume
86pub_type
杂志文章abstract::Antigen presentation by enterocytes isolated from the rat small bowel was studied by using T cell proliferation, and immunoregulatory function in an antigen-driven culture system, as indicator systems. Lymph node T cells obtained from rats immunized with ovalbumin (OA) failed to divide when cultured for 4 days in the ...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1990.52
更新日期:1990-12-01 00:00:00
abstract::The goal of this study was to further characterize the interaction between an abundant urinary glycoprotein, Tamm-Horsfall protein, and complement 1q to determine the robustness of this reaction under different environmental conditions (particularly pH) and to begin to determine the specificity of this reaction. The i...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.1440-1711.2002.01125.x
更新日期:2002-12-01 00:00:00
abstract::The role of plasmacytoid dendritic cells (pDC) in anti-HIV immunity is mostly represented by the production of type I IFN in response to HIV infection in vitro and in vivo. This production is decreased in HIV-1 infected patients at the time of primary infection and during chronic disease in association with progressio...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1111/j.1440-1711.2005.01394.x
更新日期:2005-10-01 00:00:00
abstract::Mice infected with Sarcocystis muris showed a significant reduction in plaque-forming cells (PFC) and delayed-type hypersensitivity (DHS) responses to an unrelated protein antigen, bovine gamma-globulin, when compared with uninfected controls. This immunosuppression was observed only when infection preceded immunizati...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1988.26
更新日期:1988-01-01 00:00:00
abstract::Previous data from this laboratory have shown that fluorescein-specific cytotoxic T cells derived from naive mice are capable of distinguishing between different isomeric forms of the fluorescein hapten, as well as between the iodoacetamido-, isothiocyanate- and dichlorotriazinyl amino-fluorescein derivatives. In this...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1995.24
更新日期:1995-04-01 00:00:00
abstract::CD4 T cells play a key role in immunological memory. We have demonstrated that professional memory CD4 T cells reside and rest in the bone marrow (BM). However, the molecular mechanisms of their establishment in the BM and their maintenance remain unclear. We here show that memory CD4 T cells express high levels of CD...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2013.36
更新日期:2013-09-01 00:00:00
abstract::Human cytomegalovirus (HCMV), the β-herpesvirus prototype, has evolved a wide spectrum of mechanisms to counteract host immunity. Among them, HCMV uses cellular captured genes encoding molecules capable of interfering with the original host function or of fulfilling new immunomodulatory tasks. Here, we report on UL7, ...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2011.55
更新日期:2011-10-01 00:00:00
abstract::Inhaled allergens are known for their immediate and ongoing effects in the respiratory tract (RT). In this report, we track inhaled antigen in normal mice for 7 days and find that while it is cleared from the airways, inhaled antigen persists in peripheral lung tissue and the draining lymph nodes (DLNs). The persisten...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2010.18
更新日期:2010-08-01 00:00:00
abstract::Activin A, a member of the transforming growth factor-β superfamily, is a critical early mediator of acute inflammation. Activin A release coincides with the release of tumour necrosis factor-α (TNF-α) in models of lipopolysaccharide (LPS)-induced inflammation. The source of circulating activin A during acute inflamma...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2011.12
更新日期:2011-11-01 00:00:00
abstract::Tamm-Horsfall protein (THP) binds strongly to complement 1q (C1q), a key component of the classical complement pathway. The goals of this study were to determine whether THP altered the activation of the classical complement pathway and whether the carbohydrate portion of THP was involved in this glycoprotein's bindin...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/j.1440-1711.2006.01434.x
更新日期:2006-08-01 00:00:00
abstract::CD4(+) T cells are activated upon recognition of peptide antigen in the context of MHC class II molecules, expressed by specialized APC. In this study, we show that CD4(+) T cells cross-compete for antigenic complexes on the surface of APC, inhibiting activation of other potentially reactive T cells of the same and di...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.0818-9641.2004.01233.x
更新日期:2004-04-01 00:00:00
abstract::The mammalian testis is an immunoprivileged organ where male germ cell autoantigens are immunologically ignored. Both systemic immune tolerance to autoantigens and local immunosuppressive milieu contribute to the testicular immune privilege. Testicular immunosuppression has been intensively studied, but information on...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2014.97
更新日期:2015-03-01 00:00:00
abstract::A hypothesis if formulated for the mode of action of the 'atopy gene': the gene(s) causing an increased tendency to mount an IgE immune response to trivial environmental antigens. It is postulated that some antigens are not efficiently transported to the lymphoid organs, the location of the 'eutopic' immune system; mi...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.1996.28
更新日期:1996-04-01 00:00:00
abstract::In their recent publication, Kuczma and colleagues have provided evidence that advances the relationship between naive T cells, T cell anergy and T regulatory cells. Their findings strengthen the understanding of how these T cell subsets function in relation to self and microbiota-derived epitopes to promote and maint...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/imcb.12424
更新日期:2020-12-04 00:00:00
abstract::The germinal centre reaction (GCR) is a fundamental component of the immune response to T-dependent antigens, during which the immunoglobulin (Ig) genes of B cells experience somatic hypermutation and selection. A maximum-likelihood method on DNA sequence data from 16 individual germinal centres was used to infer that...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1046/j.1440-1711.1998.00753.x
更新日期:1998-08-01 00:00:00
abstract::Several histone deacetylases (HDACs) are involved in the regulation of forkhead box protein P3 (FOXP3) expression and function by affecting features of FOXP3 protein stability. FOXP3, a forkhead family transcription factor specially expressed in regulatory T (Treg) cells, controls the expression of many key immune-reg...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.2011.101
更新日期:2012-01-01 00:00:00
abstract::There is an urgent need for new, powerful adjuvants suitable for use with sub-unit and peptide vaccines in humans. We have measured the humoral immune response in BALB/c mice to vaccine formulations using recombinant HBsAg antigens, and gamma inulin and alum adjuvants. Using Merck, Sharpe & Dohme (MSD) HBsAg at 10 mic...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1990.15
更新日期:1990-04-01 00:00:00
abstract::The trace element zinc is essential for the survival and function of all cells. Zinc deficiency, whether nutritional or genetic, is fatal if left untreated. The effects of zinc deficiency are particularly obvious in the skin, seen as an erythematous rash, scaly plaques, and ulcers. Electron microscopy reveals degenera...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/j.1440-1711.2005.01391.x
更新日期:2006-02-01 00:00:00
abstract::The function of mast cells in allergic and organ-specific autoimmune responses is highly controversial. In the current study, we aimed to dissect the role of mast cells in systemic autoimmunity in the B6(lpr/lpr) mouse, a spontaneous model of systemic lupus erythematosus. B6(lpr/lpr) mice were interbred with C57Bl/6-K...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2015.49
更新日期:2015-11-01 00:00:00
abstract::FOXP3+ regulatory T (Treg) cells are indispensable for immune homeostasis, but their study in humans is complicated by heterogeneity within Treg, the difficulty in purifying Tregs using surface marker expression (e.g. CD25) and the transient expression of FOXP3 by activated effector cells. Here, we report that express...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.2015.90
更新日期:2016-03-01 00:00:00
abstract::It is shown how Ig specificities, randomly generated in conventional B cells, come to be expressed in the genetically-determinate B1 population. Thus the adaptive antibody population facilitates the evolution of the natural antibody repertoire, in accordance with the Baldwin effect in the evolution of instinct. The ev...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.1996.50
更新日期:1996-06-01 00:00:00
abstract::Tumour necrosis factor (TNF) is a highly potent, proinflammatory cytokine with broad-ranging functions from the regulation of endothelial cell adhesion molecules to facilitate entry of leucocytes into tissues, to direct induction of cellular cytotoxicity. This diversity of function potentially attributable to TNF in t...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.1996.77
更新日期:1996-10-01 00:00:00
abstract::MicroRNAs (miRNAs) are abundant small molecules of ≈ 22 nucleotides that reprogram gene expression by targeting mRNA degradation and translation disruption. An emerging concept implicates miRNA coupling with transcription factors in myeloid-based development of dendritic cells, monocytes and granulocytes, as well as f...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.2011.74
更新日期:2012-07-01 00:00:00
abstract::Ikaros, Aiolos and Helios encode zinc finger transcription factors that are important regulators of lymphoid development and differentiation. These proteins are involved in the control of gene expression and when associated with nuclear complexes, participate in nucleosome remodeling. Because differential splicing pro...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1046/j.1440-1711.2003.01159.x
更新日期:2003-06-01 00:00:00
abstract::Depending on the microenvironment conditions, macrophages display phenotypic and functional heterogeneity. This study characterized the programmed cell death-ligand 2 (PD-L2)-expressing macrophage-like cells drained from surgical wound zones, and investigated their influence on helper T (Th) cell responses. Although a...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1111/imcb.12310
更新日期:2020-02-01 00:00:00
abstract::The multimammate rat Mastomys natalensis, when infected with the filarial parasite Acanthocheilonema viteae, develops amicrofilaraemia. Worm recovery and the duration and intensity of microfilaraemia were analysed and related to the humoral and cellular immune responses of the host by using an antibody-dependent cell-...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1990.3
更新日期:1990-02-01 00:00:00
abstract::Epstein-Barr virus achieves its ubiquitous and uniform epidemiological distribution by a dual strategy of latency to guarantee lifelong persistence and intermittent replication to guarantee transmission. These two functions appear to dictate residence in different cell types: latency in B lymphocytes and replication i...
journal_title:Immunology and cell biology
pub_type: 杂志文章,评审
doi:10.1038/icb.1995.79
更新日期:1995-12-01 00:00:00
abstract::This paper reports the production and characterization of three monoclonal antibodies (mAb) recognizing ovine vascular cell adhesion molecule-1 (VCAM-1). The mAb were raised against sheep umbilical vein endothelial cells (ShUVEC) and flow cytometric analysis demonstrated that one mAb, QE4G9, was cross-reactive with hu...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1997.85
更新日期:1997-12-01 00:00:00
abstract::T cell proliferative responses to rye and Bermuda grass pollen allergens have been studied in a series of 51 atopic and 18 non-atopic subjects. Mean T cell responses were higher in the atopic group than in the non-atopic group (P < 0.001), and there was a strong correlation between the magnitude of reaction in the T c...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1995.3
更新日期:1995-02-01 00:00:00
abstract::Adult Nematospiroides dubius excretory-secretory (ES) products were collected from worms cultured in vitro, radiolabelled and separated by sodium dodecyl polyacrylamide gel electrophoresis (SDS-PAGE). The components were characterized and assessed for molecular weight (MW) after autoradiography and gel staining, for a...
journal_title:Immunology and cell biology
pub_type: 杂志文章
doi:10.1038/icb.1989.16
更新日期:1989-04-01 00:00:00