Abstract:
BACKGROUND:Myeloid derived suppressor cells (MDSCs) present a significant obstacle to cancer immunotherapy because they dampen anti-tumor cytotoxic T cell responses. Previous groups, including our own, have reported on the myelo-depletive effects of certain chemotherapy agents. We have shown previously that decitabine increased tumor cell Class I and tumor antigen expression, increased ability of tumor cells to stimulate T lymphocytes, depleted tumor-induced MDSC in vivo and augmented immunotherapy of a murine mammary carcinoma. RESULTS:In this study, we expand upon this observation by testing a next-generation DNA methyltransferase inhibitor (DNMTi), guadecitabine, which has increased stability in the circulation. Using the 4 T1 murine mammary carcinoma model, in BALB/cJ female mice, we found that guadecitabine significantly reduces tumor burden in a T cell-dependent manner by preventing excessive myeloid proliferation and systemic accumulation of MDSC. The remaining MDSC were shifted to an antigen-presenting phenotype. Building upon our previous publication, we show that guadecitabine enhances the therapeutic effect of adoptively transferred antigen-experienced lymphocytes to diminish tumor growth and improve overall survival. We also show guadecitabine's versatility with similar tumor reduction and augmentation of immunotherapy in the C57BL/6 J E0771 murine breast cancer model. CONCLUSIONS:Guadecitabine depleted and altered MDSC, inhibited growth of two different murine mammary carcinomas in vivo, and augmented immunotherapeutic efficacy. Based on these findings, we believe the immune-modulatory effects of guadecitabine can help rescue anti-tumor immune response and contribute to the overall effectiveness of current cancer immunotherapies.
journal_name
BMC Immunoljournal_title
BMC immunologyauthors
Luker AJ,Graham LJ,Smith TM Jr,Camarena C,Zellner MP,Gilmer JS,Damle SR,Conrad DH,Bear HD,Martin RKdoi
10.1186/s12865-020-0337-5subject
Has Abstractpub_date
2020-02-27 00:00:00pages
8issue
1issn
1471-2172pii
10.1186/s12865-020-0337-5journal_volume
21pub_type
杂志文章相关文献
BMC IMMUNOLOGY文献大全abstract:BACKGROUND:The functional immaturity of T cells contributes to the susceptibility of neonates to infections and the less severe graft-versus-host disease associated with cord blood (CB) transplantation. We have previously reported that insulin-like growth factor - I (IGF-I) promotes the phytohaemagglutinin (PHA)-induce...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-9-74
更新日期:2008-12-17 00:00:00
abstract:BACKGROUND:Down syndrome (DS) is the most common syndromic immunodeficiency with an increased risk of infection, mortality from sepsis, and autoinflammation. Innate immune function is altered in DS and therefore we examined responses in CD11b and Toll like receptor 4 (TLR-4), which are important immune cell surface mar...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-018-0270-z
更新日期:2018-11-03 00:00:00
abstract:BACKGROUND:Proinflammatory genes are highly expressed in several metabolic disorders associated with obesity. But it is not clarified whether gene expression levels and downstream inflammatory markers are related to the metabolic state or the presence of obesity. Hence, the present study aimed to compare Toll-Like Rece...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-019-0303-2
更新日期:2019-07-04 00:00:00
abstract:BACKGROUND:We have recently demonstrated that all-trans-retinoic acid (ATRA) and 9-cis-retinoic acid (9-cis RA) promote IL-4, IL-5 and IL-13 synthesis, while decreasing IFN-gamma and TNF-alpha expression by activated human T cells and reduces the synthesis of IL-12p70 from accessory cells. Here, we have demonstrated th...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-9-16
更新日期:2008-04-16 00:00:00
abstract:BACKGROUND:Cryopreservation of peripheral blood mononuclear cells (PBMCs) is a common and essential practice in conducting research. There are different reports in the literature as to whether cryopreserved PBMCs need to only be stored ≤ -150 °C or can be stored for a specified time at -80 °C. Therefore, we performed g...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-016-0144-1
更新日期:2016-03-15 00:00:00
abstract:BACKGROUND:Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder characterized by defective function of Fas, autoimmune manifestations that predominantly involve blood cells, polyclonal accumulation of lymphocytes in the spleen and lymph nodes with lymphoadenomegaly and/or splenomegaly, and expans...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-8-28
更新日期:2007-11-13 00:00:00
abstract:BACKGROUND:Immunoglobulin rearrangement involves random and imprecise processes that act to both create and constrain diversity. Two such processes are the loss of nucleotides through the action of unknown exonuclease(s) and the addition of P nucleotides. The study of such processes has been compromised by difficulties...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-5-19
更新日期:2004-09-02 00:00:00
abstract:BACKGROUND:Impaired diabetic wound healing occurs as a consequence of excessive reactive oxygen species (ROS) and inflammatory cytokine production. We previously found that whey protein (WP) was able to normally regulate the ROS and inflammatory cytokines during the inflammatory phase (first day) in streptozotocin (STZ...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-14-31
更新日期:2013-07-25 00:00:00
abstract:BACKGROUND:Macrophages are key players in the initiation, perpetuation and regulation of both innate and adaptive immune responses. They largely perform these roles through modulation of the expression of genes, especially those encoding cytokines. Murine bone marrow derived macrophages (BMDMs) are commonly used as a m...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-017-0223-y
更新日期:2017-10-03 00:00:00
abstract:BACKGROUND:Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by the novel coronavirus SARS-CoV. The T cell epitopes of the SARS CoV spike protein are well known, but no systematic evaluation of the functional and structural roles of each residue has been reported for these antigenic epit...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-13-50
更新日期:2012-09-10 00:00:00
abstract:BACKGROUND:Pro-inflammatory cytokines can affect intracellular lipid metabolism. A variety of effects have been described for different cell types; hepatocyte lipid turnover pathways are inhibited during inflammation, whereas interleukin-1beta (IL-1beta) reduces intracellular cholesterol levels in fibroblasts. Levels o...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-9-70
更新日期:2008-11-25 00:00:00
abstract:BACKGROUND:To understand the role of genetic factors on chromosome 1 in the regulation of spontaneous arthritis in mice deficient in IL-1 receptor antagonist protein (IL_1RA), we previously used speed congenic breeding to transfer the QTL region from DBA/1(-/-) mice that are resistant to spontaneous arthritis into BALB...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-014-0057-9
更新日期:2014-12-09 00:00:00
abstract:BACKGROUND:Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensa...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-10-54
更新日期:2009-10-08 00:00:00
abstract:BACKGROUND:T-cells extravasation and CNS parenchyma infiltration during autoimmune neurodegenerative disease can be evoked by local antigen presenting cells. Studying the chemoattracting potential of spinal perivascular macrophages (SPM) during experimental allergic encephalomyelitis (EAE), we observed numerous infiltr...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-3-11
更新日期:2002-08-26 00:00:00
abstract:BACKGROUND:While tumor necrosis factor alpha (TNF-α) inhibitors (TNFi) and other biologics are very effective against autoimmune diseases, they can also cause infectious diseases. Therefore, it is important to clarify whether the TNFi sometimes used to treat patients with rheumatoid arthritis (RA) complicated with huma...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-017-0191-2
更新日期:2017-02-03 00:00:00
abstract:BACKGROUND:Parasite-specific IgE levels correlate with human resistance to reinfection with Schistosoma spp. after chemotherapy. Although the role of eosinophils in schistosomiasis has been the focus of a great deal of important research, the involvement of other Fcepsilon receptor-bearing cells, such as mast cells and...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-5-6
更新日期:2004-04-21 00:00:00
abstract:BACKGROUND:Burkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas. We recently showed that NADPH oxidase but not nitric oxide (NO) contributes to resistance in innately resistant C57BL/6 mice in a B. pseudomallei respiratory infection ...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-12-20
更新日期:2011-03-16 00:00:00
abstract:BACKGROUND:Macrophages have heterogeneous phenotypes and complex functions within both innate and adaptive immune responses. To date, most experimental studies have been performed on macrophages derived from bone marrow, spleen and peritoneum. However, differences among macrophages from these particular sources remain ...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-14-6
更新日期:2013-02-05 00:00:00
abstract:BACKGROUND:The need for rapid and accurate comparison of panels of adjuvanted vaccine formulations and subsequent rational down selection, presents several challenges for modern vaccine development. Here we describe a method which may enable vaccine and adjuvant developers to compare antigen/adjuvant combinations in a ...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-018-0245-0
更新日期:2018-01-31 00:00:00
abstract:BACKGROUND:The extracellular domains of cytokine receptors are released during inflammation, but little is known about the shedding of Toll-like receptors (TLR) and whether they can be used as diagnostic biomarkers. METHODS:The release of sTLR2 and sTLR4 was studied in in-vitro stimulations, as well as in-vivo during ...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-014-0055-y
更新日期:2014-11-19 00:00:00
abstract:BACKGROUND:The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis. The present study was undertaken to assess the effects of CP690,550 on cytokine production and cellular signaling in human CD4(+) T cells. RESULTS:CD4(+) T cells produced IL-2, IL-4, IL-17, IL-22 and IFN-γ in fol...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-12-51
更新日期:2011-08-31 00:00:00
abstract:BACKGROUND:Human tonsils are a rich source of B lymphocytes exhibiting a variety of phenotypes and activation states. Existing methods of purification are time consuming or costly. The aim of the present study was to optimize conditions to isolate large numbers of highly purified primary B lymphocytes from tonsils in a...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-10-30
更新日期:2009-05-27 00:00:00
abstract:BACKGROUND:Recent studies have shown that early growth response 2 (EGR2) is highly induced in activated T cells and regulates T cell functions. In normal C57BL/6 (B6) mice, deletion of EGR2 in lymphocytes results in the development of lupus-like systemic autoimmune disease, which implies indirectly an autoimmune protec...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-020-00370-z
更新日期:2020-07-09 00:00:00
abstract:BACKGROUND:Vascular calcification is often associated with chronic inflammation and is a risk factor for brain arterial stiffness. Our previous results showed that miR32-5p was positively correlated with vascular smooth muscle cells (VSMC) calcification, but it is unclear whether miR32-5p promoted VSMC calcification by...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-019-0324-x
更新日期:2020-01-17 00:00:00
abstract:BACKGROUND:Bv8, prokineticin-1, or endocrine gland-vascular endothelial growth factor, and prokineticin-2 are recently isolated peptide agonists of two G protein-coupled receptors, prokineticin receptor-1 (PROKR 1) and PROKR 2, and have been described as affecting a number of myeloid cell functions. We evaluated the im...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-9-60
更新日期:2008-10-28 00:00:00
abstract:BACKGROUND:Toll-like receptor 2 (TLR2) plays a critical role in mediating inflammatory/immune responses against bacterial pathogens in lung. Streptococcus pneumoniae (S. pneumoniae) and nontypeable Haemophilus influenzae (NTHi) were previously reported to synergize with each other to induce inflammatory responses. Desp...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-9-40
更新日期:2008-07-29 00:00:00
abstract:BACKGROUND:The initiation of highly active antiretroviral therapy (HAART) plays a significant role in the clinical management of HIV infected people by preventing morbidity and mortality. This benefit becomes, the most terrible when treatment failure develops. Thus, this research aims to assess the prevalence and assoc...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-018-0278-4
更新日期:2018-12-17 00:00:00
abstract:BACKGROUND:The potential utility of dendritic cells (DC) as cancer vaccines has been established in early trials in human cancers. The concomitant administration of cytotoxic agents and DC vaccines has been previously avoided due to potential immune suppression by chemotherapeutics. Recent studies show that common chem...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-11-14
更新日期:2010-03-19 00:00:00
abstract:BACKGROUND:Some chemicals, including some phthalate plasticizers, have been shown to have an adjuvant effect in mice. However, an adjuvant effect, defined as an inherent ability to stimulate the humoral immune response, was only observed after exposure to a limited number of the phthalates. An adjuvant effect may be du...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/1471-2172-9-61
更新日期:2008-10-31 00:00:00
abstract:BACKGROUND:Understanding immune mechanisms, particularly the role of innate immune markers during latent TB infection remains elusive. The main objective of this study was to evaluate mRNA gene expression patterns of toll-like receptors (TLRs) as correlates of immunity during latent TB infection and further infer their...
journal_title:BMC immunology
pub_type: 杂志文章
doi:10.1186/s12865-021-00400-4
更新日期:2021-01-28 00:00:00