Abstract：
:Epigenetic regulation of gene expression in cancer cells has been extensively studied in recent decades, resulting in the FDA approval of multiple epigenetic agents for treating different cancer types. Recent studies have revealed novel roles of epigenetic dysregulation in altering the phenotypes of immune cells and tumor-associated stromal cells, including fibroblasts and endothelial cells. As a result, epigenetic dysregulation of these cells reshapes the tumor microenvironment (TME), changing it from an antitumor environment to an immunosuppressive environment. Here, we review recent studies demonstrating how specific epigenetic mechanisms drive aspects of stromal and immune cell differentiation with implications for the development of solid tumor therapeutics, focusing on the pancreatic ductal adenocarcinoma (PDA) TME as a representative of solid tumors. Due to their unique ability to reprogram the TME into a more immunopermissive environment, epigenetic agents have great potential for sensitizing cancer immunotherapy to augment the antitumor response, as an immunopermissive TME is a prerequisite for the success of cancer immunotherapy but is often not developed with solid tumors. The idea of combining epigenetic agents with cancer immunotherapy has been tested both in preclinical settings and in multiple clinical trials. In this review, we highlight the basic biological mechanisms underlying the synergy between epigenetic therapy and immunotherapy and discuss current efforts to translate this knowledge into clinical benefits for patients.
journal_name
Cell Mol Immunoljournal_title
Cellular & molecular immunologyauthors
Pan X,Zheng Ldoi
10.1038/s41423-020-0505-9subject
Has Abstractpub_date
2020-09-01 00:00:00pages
940-953issue
9eissn
1672-7681issn
2042-0226pii
10.1038/s41423-020-0505-9journal_volume
17pub_type
杂志文章,评审abstract：:The type 2 immune response is critical for host defense against large parasites such as helminths. On the other hand, dysregulation of the type 2 immune response may cause immunopathological conditions, including asthma, atopic dermatitis, rhinitis, and anaphylaxis. Thus, a balanced type 2 immune response must be achi...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/s41423-019-0210-8
更新日期：2019-03-01 00:00:00
abstract：:We generated a human dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) transgenic mouse in which renal tubular epithelial cells expressed DC-SIGN. The transgenic mice were infected with Candida albicans intravenously to study how DC-SIGN expression affected the pathogenesis of systemic candidiasis. We dis...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/s41423-018-0161-5
更新日期：2019-03-01 00:00:00
abstract：:In previous research, chimerical BPI23-Fcgamma1 gene which consisted of human bactericidal/permeability increasing protein (BPI) gene of encoding the functional N terminus (amino acid residues 1 to 199) of human BPI and Fcgamma1 gene of encoding the Fc segment of human immunoglobulin G1 was successfully reconstructed ...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/cmi.2008.55
更新日期：2008-12-01 00:00:00
abstract：:To construct cDNA library of nasopharyngeal carcinoma (NPC) and obtain the NPC associated or specific antigens from it, we used a powerful new method to identify the antigens eliciting humoral immune response, which is SEREX (serological identification of antigen by recombinant cDNA expression library). Autologous ser...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：
更新日期：2006-02-01 00:00:00
abstract：:Previously, we demonstrated that macrophages from thrombospondin 1 (TSP1)-deficient mice have a reduced inflammatory phenotype, suggesting that TSP1 plays a role in macrophage activation. In this study, we determined how TSP1 regulates macrophage function. We found that recombinant or purified platelet human TSP1 trea...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/cmi.2013.32
更新日期：2013-11-01 00:00:00
abstract：:Viral RNAs produced during viral infection are recognized by the cytoplasmic RNA helicases retinoic acid-inducible gene-I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5). A central adapter protein downstream of RIG-I and MDA5 is the mitochondrial membrane protein virus-induced signaling adaptor (VISA), w...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/cmi.2010.36
更新日期：2010-09-01 00:00:00
abstract：:Infection with human immunodeficiency virus (HIV) disrupts the balance among γδ T cell subsets, with increasing Vδ1+ cells and substantial depletion of circulating Vδ2+ cells. Depletion is an indirect effect of HIV in CD4-negative Vδ2 cells, but is specific for phosphoantigen-responsive subpopulations identified by th...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/cmi.2012.50
更新日期：2013-01-01 00:00:00
abstract：:Transplantation of mesenchymal stem cells (MSCs) has been recently studied in animal models, and in clinical trials of patients with fulminant hepatic failure, end-stage liver diseases and inherited metabolic disorders. Modulatory cytokines produced by MSCs can inhibit immunocyte proliferation and migration to the liv...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/cmi.2010.57
更新日期：2011-01-01 00:00:00
abstract：:Among various immunoregulatory molecules, the B7 family of immune-checkpoint receptors consists of highly valuable targets for cancer immunotherapy. Antibodies targeting two B7 family co-inhibitory receptors, CTLA-4 and PD-1, have elicited long-term clinical outcomes in previously refractory cancer types and are consi...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/cmi.2017.148
更新日期：2018-05-01 00:00:00
abstract：:Recombinant human prolactin (rhPRL) was administered to huPBL-SCID mice to determine its effects on human immunologic reconstitution and function. The huPBL-SCID mice were given 10 microg i.p. injection of rhPRL every other day for a total of 10 injections after huPBL were transferred. The results demonstrated that rh...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：
更新日期：2004-04-01 00:00:00
abstract：:Organ transplantation is an effective therapeutic tool for treating many terminal diseases. However, one of the biggest challenges of transplantation is determining how to achieve the long-term survival of the allogeneic or xenogeneic transplant by, for example, preventing transplant rejection. In the current study, C...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/s41423-018-0009-z
更新日期：2019-06-01 00:00:00
abstract：:Previous studies have shown that the CC chemokine receptor CCR5 is downregulated on monocyte/macrophage (MO/Mphi) surfaces in head and neck squamous cell carcinoma (HNSCC) patients (stage IIIB). Ligands (RANTES, MIP-1alpha and MIP-1beta) of this chemokine receptor were also secreted in lesser quantity from MO/Mphi of ...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/cmi.2010.29
更新日期：2010-09-01 00:00:00
abstract：:Exercise at regular intervals is assumed to have a positive effect on immune functions. Conversely, after spaceflight and under simulated weightlessness (e.g., bed rest), immune functions can be suppressed. We aimed to assess the effects of simulated weightlessness (Second Berlin BedRest Study; BBR2-2) on immunologica...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,随机对照试验
doi：10.1038/cmi.2014.106
更新日期：2015-07-01 00:00:00
abstract：:Inflammasomes are multi-protein signaling complexes that trigger the activation of inflammatory caspases and the maturation of interleukin-1β. Among various inflammasome complexes, the NLRP3 inflammasome is best characterized and has been linked with various human autoinflammatory and autoimmune diseases. Thus, the NL...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/cmi.2015.95
更新日期：2016-03-01 00:00:00
abstract：:Epigenetic modifications to histones dictate the differentiation of naïve CD4+ T cells into different subsets of effector T helper (TH) cells. The histone methyltransferase enhancer of zeste homolog 2 (EZH2) has been implicated in the mechanism regulating the differentiation of TH1, TH2 and regulatory T (Treg) cells. ...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/s41423-019-0219-z
更新日期：2020-03-01 00:00:00
abstract：:Dendritic cells (DCs) are the most potent professional antigen-presenting cells, and capable of stimulating naïve T cells and driving primary immune responses. DCs are poised to capture antigen, migrate to draining lymphoid organs, and after a process of maturation, select antigen-specific lymphocytes to which they pr...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：
更新日期：2006-06-01 00:00:00
abstract：:Neonates are at increased risk of viral encephalopathies that can result in neurological dysfunction, seizures, permanent disability and even death. The neurological damage results from the combined effect of the virus and the immune response it elicits, thus finding tools to facilitate viral clearance from central ne...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/cmi.2016.41
更新日期：2017-01-01 00:00:00
abstract：:MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs, and changes in miRNAs are involved in tumor origin and progression. Studies have shown that miR-20a is overexpressed in human ovarian cancer tissues and that this miRNA enhances long-term cellular proliferation and invasion capabilities. In this study...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/cmi.2014.30
更新日期：2014-09-01 00:00:00
abstract：:Patients with primary ciliary dyskinesia (PCD) and cystic fibrosis (CF), two inherited disorders, suffer from recurrent airway infections characterized by persistent bacterial colonization and uncontrollable inflammation. Although present in high counts, neutrophils fail to clear infection in the airways. High levels ...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/cmi.2017.118
更新日期：2018-04-01 00:00:00
abstract：:The major limitation for the maturation of dendritic cells (DCs) using Toll-like receptor (TLR) agonists is their decreased ability to migrate into lymph nodes compared with conventional DCs. CD38 can be used as a multifunctional marker to modulate migration, survival and Th1 responses of DCs. CD74 has been shown to n...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/cmi.2011.7
更新日期：2011-07-01 00:00:00
abstract：:CD8(+) natural killer T (NKT) cells from EBV-associated tumour patients are quantitatively and functionally impaired. EBV-induced CD8(+) NKT cells drive syngeneic T cells into a Th1-bias response to suppress EBV-associated malignancies. IL-4-biased CD4(+) NKT cells do not affect either syngeneic T cell cytotoxicity or...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/cmi.2009.48
更新日期：2009-10-01 00:00:00
abstract：:An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title：Cellular & molecular immunology
pub_type： 已发布勘误
doi：10.1038/s41423-019-0332-z
更新日期：2020-03-01 00:00:00
abstract：:Induction of osteopontin (OPN), a well-known pro-inflammatory molecule, has been observed in acetaminophen (APAP)-induced hepatotoxicity. However, the precise cell source for OPN induction and its role during APAP-induced hepatotoxicity has not been fully explored. By employing a hepatotoxic mouse model induced by APA...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：10.1038/s41423-018-0033-z
更新日期：2019-05-01 00:00:00
abstract：:It is well-documented that alcohol drinking together with hepatitis viral infection accelerates liver injury; however the underlying mechanisms remain unknown. In this paper, we demonstrated that primary hepatocytes from transgenic mice overexpressing hepatitis B virus X protein (HBX) were more susceptible to ethanol-...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：
更新日期：2005-02-01 00:00:00
abstract：:Cytomegaloviruses (CMVs), members of the herpesvirus family, have evolved a variety of mechanisms to evade the immune response to survive in infected hosts and to establish latent infection. They effectively hide infected cells from the effector mechanisms of adaptive immunity by eliminating cellular proteins (major h...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/cmi.2014.85
更新日期：2015-03-01 00:00:00
abstract：:Follicular helper T (Tfh) cells select mutated B cells in germinal centres, which can then differentiate into long-lived high affinity memory B cells and plasma cells. Tfh cells are regulated by a unique molecular programme orchestrated by the transcriptional repressor Bcl6. This transcription factor turns down expres...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/cmi.2010.18
更新日期：2010-05-01 00:00:00
abstract：:To evaluate the balance status of interleukin 18 (IL-18) and interleukin 18 binding protein (IL-18BP) in circulation in patients with lupus nephritis (LN) and primary nephrotic syndrome (PNS), plasma levels as well as mRNA expression in peripheral blood mononuclear cells (PBMCs) of IL-18 and IL-18BP were measured by E...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：
更新日期：2006-08-01 00:00:00
abstract：:The capacity of pluri-potent stem cells to repair the tissues in which stem cells reside holds great promise in development of novel cell replacement therapeutics for treating chronic and degenerative diseases. However, numerous reports show that stem cell therapy, even in an autologous setting, triggers lymphocyte in...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：
更新日期：2007-06-01 00:00:00
abstract：:Tumor necrosis factor alpha (TNF-alpha) has been recognized as an activator of nuclear factor kappaB (NF-kappaB), a factor implicated in the protection of many cell types from apoptosis. We and others have presented evidence to suggest that Fas-induced apoptosis may be an important aspect of the resolution of inflamma...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章
doi：
更新日期：2007-02-01 00:00:00
abstract：:T follicular helper (Tfh) cells were discovered just over a decade ago as germinal centre T cells that help B cells make antibodies. Included in this role is affinity maturation and isotype switching. It is here that their functions become less clear. Tfh cells principally produce IL-21 which inhibits class switching ...
journal_title：Cellular & molecular immunology
pub_type： 杂志文章,评审
doi：10.1038/cmi.2012.31
更新日期：2012-09-01 00:00:00
