Role of Epigenetic Modifications in Inhibitory Immune Checkpoints in Cancer Development and Progression.

Abstract:

:A balance between co-inhibitory and co-stimulatory signals in the tumor microenvironment (TME) is critical to suppress tumor development and progression, primarily via maintaining effective immunosurveillance. Aberrant expression of immune checkpoints (ICs), including programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), lymphocyte-activation gene 3 (LAG-3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT), can create an immune-subversive environment, which helps tumor cells to evade immune destruction. Recent studies showed that epigenetic modifications play critical roles in regulating the expression of ICs and their ligands in the TME. Reports showed that the promoter regions of genes encoding ICs/IC ligands can undergo inherent epigenetic alterations, such as DNA methylation and histone modifications (acetylation and methylation). These epigenetic aberrations can significantly contribute to the transcriptomic upregulation of ICs and their ligands. Epigenetic therapeutics, including DNA methyltransferase and histone deacetylase inhibitors, can be used to revert these epigenetic anomalies acquired during the progression of disease. These discoveries have established a promising therapeutic modality utilizing the combination of epigenetic and immunotherapeutic agents to restore the physiological epigenetic profile and to re-establish potent host immunosurveillance mechanisms. In this review, we highlight the roles of epigenetic modifications on the upregulation of ICs, focusing on tumor development, and progression. We discuss therapeutic approaches of epigenetic modifiers, including clinical trials in various cancer settings and their impact on current and future anti-cancer therapies.

journal_name

Front Immunol

journal_title

Frontiers in immunology

authors

Saleh R,Toor SM,Sasidharan Nair V,Elkord E

doi

10.3389/fimmu.2020.01469

subject

Has Abstract

pub_date

2020-07-14 00:00:00

pages

1469

issn

1664-3224

journal_volume

11

pub_type

杂志文章,评审
  • Mechanisms of Relapse After CD19 CAR T-Cell Therapy for Acute Lymphoblastic Leukemia and Its Prevention and Treatment Strategies.

    abstract::Chimeric antigen receptor (CAR) T-cell therapy is highly effective in the treatment of B-cell acute lymphoblastic leukemia (ALL) or B-cell lymphoma, providing alternative therapeutic options for patients who failed to respond to conventional treatment or relapse. Moreover, it can bridge other therapeutic strategies an...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.02664

    authors: Xu X,Sun Q,Liang X,Chen Z,Zhang X,Zhou X,Li M,Tu H,Liu Y,Tu S,Li Y

    更新日期:2019-11-12 00:00:00

  • IL-23 Contributes to Campylobacter jejuni-Induced Intestinal Pathology via Promoting IL-17 and IFNγ Responses by Innate Lymphoid Cells.

    abstract::Human pathogen Campylobacter jejuni is a significant risk factor for the development of long-term intestinal dysfunction although the cellular and molecular mechanisms remain scantily defined. IL-23 is an emerging therapeutic target for the treatment of inflammatory intestinal diseases, however its role in C. jejuni-d...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.579615

    authors: Jing X,Korchagina AA,Shein SA,Muraoka WT,Koroleva E,Tumanov AV

    更新日期:2021-01-06 00:00:00

  • B7/CD28 in central tolerance: costimulation promotes maturation of regulatory T cell precursors and prevents their clonal deletion.

    abstract::According to the "two-step model," the intrathymic generation of CD4⁺ regulatory T (T(reg)) cells segregates into a first, T cell receptor (TCR)-driven phase and a second, cytokine-dependent phase. The initial TCR stimulus gives rise to a CD25⁺Foxp3⁻ developmental intermediate. These precursors subsequently require cy...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2011.00030

    authors: Hinterberger M,Wirnsberger G,Klein L

    更新日期:2011-07-25 00:00:00

  • Exploring Synergy in Combinations of Tumor-Derived Vaccines That Harbor 4-1BBL, OX40L, and GM-CSF.

    abstract::Recent studies have demonstrated that combination of modulatory immune strategies may potentiate tumor cell elimination. Most strategies rely on the use of monoclonal antibodies that can block cell surface receptors to overcome tumor-induced immunosuppression or acting as costimulatory ligands to boost activation of T...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01150

    authors: Manrique-Rincón AJ,Beraldo CM,Toscaro JM,Bajgelman MC

    更新日期:2017-09-19 00:00:00

  • Chronic intestinal inflammation: inflammatory bowel disease and colitis-associated colon cancer.

    abstract::The inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are chronic inflammatory disorders of the intestine. The prevalence in the United States is greater than 200 cases per 100,000, with the total number of IBD patients between 1 and 1.5 million. CD may affect all parts of ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00107

    authors: Rubin DC,Shaker A,Levin MS

    更新日期:2012-05-08 00:00:00

  • Effective Targeting of TAG72+ Peritoneal Ovarian Tumors via Regional Delivery of CAR-Engineered T Cells.

    abstract::Impressive clinical efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy for hematological malignancies have prompted significant efforts in achieving similar responses in solid tumors. The lack of truly restricted and uniform expression of tumor-associated antigens, as well as limited T cell persiste...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2018.02268

    authors: Murad JP,Kozlowska AK,Lee HJ,Ramamurthy M,Chang WC,Yazaki P,Colcher D,Shively J,Cristea M,Forman SJ,Priceman SJ

    更新日期:2018-11-19 00:00:00

  • Corrigendum: TLR2 Expression in Peripheral CD4+ T Cells Promotes Th17 Response and Is Associated with Disease Aggravation of Hepatitis B Virus-Related Acute-On-Chronic Liver Failure.

    abstract::[This corrects the article DOI: 10.3389/fimmu.2017.01609.]. ...

    journal_title:Frontiers in immunology

    pub_type: 已发布勘误

    doi:10.3389/fimmu.2020.01566

    authors: Xu C,Lu Y,Zheng X,Feng X,Yang X,Timm J,Wu J,Wang B,Lu M,Yang D,Liu J

    更新日期:2020-07-24 00:00:00

  • Viral Evasion of the Complement System and Its Importance for Vaccines and Therapeutics.

    abstract::The complement system is a key component of innate immunity which readily responds to invading microorganisms. Activation of the complement system typically occurs via three main pathways and can induce various antimicrobial effects, including: neutralization of pathogens, regulation of inflammatory responses, promoti...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01450

    authors: Mellors J,Tipton T,Longet S,Carroll M

    更新日期:2020-07-09 00:00:00

  • The Joint-Brain Axis: Insights From Rheumatoid Arthritis on the Crosstalk Between Chronic Peripheral Inflammation and the Brain.

    abstract::Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive polyarthritis. Beyond joint pathology, RA is associated with neuropsychiatric comorbidity including depression, anxiety, and an increased risk to develop neurodegenerative diseases in later life. Studies investigating the central nerv...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.612104

    authors: Süß P,Rothe T,Hoffmann A,Schlachetzki JCM,Winkler J

    更新日期:2020-12-10 00:00:00

  • Prefusion RSV F Immunization Elicits Th2-Mediated Lung Pathology in Mice When Formulated With a Th2 (but Not a Th1/Th2-Balanced) Adjuvant Despite Complete Viral Protection.

    abstract::Respiratory syncytial virus (RSV) remains the most common cause of lower respiratory tract infections in children worldwide. Development of a vaccine has been hindered by the risk of developing enhanced respiratory disease (ERD) upon natural exposure to the virus. Generation of higher quality neutralizing antibodies w...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01673

    authors: Eichinger KM,Kosanovich JL,Gidwani SV,Zomback A,Lipp MA,Perkins TN,Oury TD,Petrovsky N,Marshall CP,Yondola MA,Empey KM

    更新日期:2020-07-29 00:00:00

  • Developmental and Functional Control of Natural Killer Cells by Cytokines.

    abstract::Natural killer (NK) cells are effective in combating infections and tumors and as such are tempting for adoptive transfer therapy. However, they are not homogeneous but can be divided into three main subsets, including cytotoxic, tolerant, and regulatory NK cells, with disparate phenotypes and functions in diverse tis...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00930

    authors: Wu Y,Tian Z,Wei H

    更新日期:2017-08-04 00:00:00

  • Checkpoint Blockade Toxicity and Immune Homeostasis in the Gastrointestinal Tract.

    abstract::Monoclonal antibodies targeting the regulatory immune "checkpoint" receptors CTLA-4, PD-1, and PD-L1 are now standard therapy for diverse malignancies including melanoma, lung cancer, and renal cell carcinoma. Although effective in many patients and able to induce cures in some, targeting these regulatory pathways has...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.01547

    authors: Dougan M

    更新日期:2017-11-15 00:00:00

  • α7 Nicotinic Acetylcholine Receptor Signaling Modulates Ovine Fetal Brain Astrocytes Transcriptome in Response to Endotoxin.

    abstract::Neuroinflammation in utero may result in lifelong neurological disabilities. Astrocytes play a pivotal role in this process, but the mechanisms are poorly understood. No early postnatal treatment strategies exist to enhance neuroprotective potential of astrocytes. We hypothesized that agonism on α7 nicotinic acetylcho...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01063

    authors: Cao M,MacDonald JW,Liu HL,Weaver M,Cortes M,Durosier LD,Burns P,Fecteau G,Desrochers A,Schulkin J,Antonelli MC,Bernier RA,Dorschner M,Bammler TK,Frasch MG

    更新日期:2019-05-09 00:00:00

  • Age-Based Dynamics of a Stable Circulating Cd8 T Cell Repertoire Component.

    abstract::T-cell memory to pathogens can be envisioned as a receptor-based imprint of the pathogenic environment on the naïve repertoire of clonotypes. Recurrent exposures to a pathogen inform and reinforce memory, leading to a mature state. The complexity and temporal stability of this system in man is only beginning to be ade...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01717

    authors: Naumova EN,Yassai MB,Demos W,Reed E,Unruh M,Haribhai D,Williams CB,Naumov YN,Gorski J

    更新日期:2019-08-06 00:00:00

  • Self-Damage Caused by Dysregulation of the Complement Alternative Pathway: Relevance of the Factor H Protein Family.

    abstract::The alternative pathway is a continuously active surveillance arm of the complement system, and it can also enhance complement activation initiated by the classical and the lectin pathways. Various membrane-bound and plasma regulatory proteins control the activation of the potentially deleterious complement system. Am...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.01607

    authors: Sánchez-Corral P,Pouw RB,López-Trascasa M,Józsi M

    更新日期:2018-07-12 00:00:00

  • Erythromycin treatment hinders the induction of oral tolerance to fed ovalbumin.

    abstract::The mucosal immune system is constantly exposed to antigen, whether it be food antigen, commensal bacteria, or harmful antigen. It is essential that the mucosal immune system can distinguish between harmful and non-harmful antigens, and initiate an active immune response to clear the harmful antigens, while initiating...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00203

    authors: Lambert SE,Kinder JM,Then JE,Parliament KN,Bruns HA

    更新日期:2012-07-18 00:00:00

  • Excess of Mortality in Adults and Elderly and Circulation of Subtypes of Influenza Virus in Southern Brazil.

    abstract:Purpose:In the elderly population, the influenza infection and its clinical complications are important causes of hospitalization and death, particularly, in longer-lived age. The objective of this study is to analyze the impact of influenza virus circulation on mortality in the elderly and adults, in years with differ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.01903

    authors: Freitas ARR,Donalisio MR

    更新日期:2018-01-08 00:00:00

  • Circumventricular Organs and Parasite Neurotropism: Neglected Gates to the Brain?

    abstract::Circumventricular organs (CVOs), neural structures located around the third and fourth ventricles, harbor, similarly to the choroid plexus, vessels devoid of a blood-brain barrier (BBB). This enables them to sense immune-stimulatory molecules in the blood circulation, but may also increase chances of exposure to micro...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2018.02877

    authors: Bentivoglio M,Kristensson K,Rottenberg ME

    更新日期:2018-12-11 00:00:00

  • Plasma Eicosanoid Profile in Plasmodium vivax Malaria: Clinical Analysis and Impacts of Self-Medication.

    abstract::The participation of cytokines and chemokines in Plasmodium vivax malaria (Pv-malaria) activates the immune response and thus causes the production of several inflammatory mediators. This process is already well-established, but little is known about eicosanoids in malaria physiopathology, especially in regards to inf...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.02141

    authors: Abreu-Filho PG,Tarragô AM,Costa AG,Monteiro WM,Meielles AFG,Costa TCC,Silva JS,Zambuzi FA,Gardinassi LG,Moraes LAB,Lacerda MVG,Sorgi CA,Faccioli LH,Malheiro A

    更新日期:2019-09-18 00:00:00

  • Pertussis Prevention: Reasons for Resurgence, and Differences in the Current Acellular Pertussis Vaccines.

    abstract::Pertussis is an acute respiratory disease caused by Bordetella pertussis. Due to its frequency and severity, prevention of pertussis has been considered an important public health issue for many years. The development of the whole-cell pertussis vaccine (wPV) and its introduction into the pediatric immunization schedu...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.01344

    authors: Esposito S,Stefanelli P,Fry NK,Fedele G,He Q,Paterson P,Tan T,Knuf M,Rodrigo C,Weil Olivier C,Flanagan KL,Hung I,Lutsar I,Edwards K,O'Ryan M,Principi N,World Association of Infectious Diseases and Immunological Disorders

    更新日期:2019-07-03 00:00:00

  • Endothelial Basement Membrane Laminins as an Environmental Cue in Monocyte Differentiation to Macrophages.

    abstract::Monocyte differentiation to macrophages is triggered by migration across the endothelial barrier, which is constituted by both endothelial cells and their underlying basement membrane. We address here the role of the endothelial basement membrane laminins (laminins 411 and 511) in this monocyte to macrophage switch. C...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.584229

    authors: Li L,Song J,Chuquisana O,Hannocks MJ,Loismann S,Vogl T,Roth J,Hallmann R,Sorokin L

    更新日期:2020-10-30 00:00:00

  • Borrelia burgdorferi Manipulates Innate and Adaptive Immunity to Establish Persistence in Rodent Reservoir Hosts.

    abstract::Borrelia burgdorferi sensu lato species complex is capable of establishing persistent infections in a wide variety of species, particularly rodents. Infection is asymptomatic or mild in most reservoir host species, indicating successful co-evolution of the pathogen with its natural hosts. However, infected humans and ...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2017.00116

    authors: Tracy KE,Baumgarth N

    更新日期:2017-02-20 00:00:00

  • Invariant NKT Cells From Donor Lymphocyte Infusions (DLI-iNKTs) Promote ex vivo Lysis of Leukemic Blasts in a CD1d-Dependent Manner.

    abstract::Allogeneic hematopoietic cell transplantation (allo-HCT) is a curative treatment option for hematologic malignancies but relapse remains the most common cause of death. Infusion of donor lymphocytes (DLIs) can induce remission and prolong survival by exerting graft-vs.-leukemia (GVL) effects. However, sufficient tumor...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.01542

    authors: Jahnke S,Schmid H,Secker KA,Einhaus J,Duerr-Stoerzer S,Keppeler H,Schober-Melms I,Baur R,Schumm M,Handgretinger R,Bethge W,Kanz L,Schneidawind C,Schneidawind D

    更新日期:2019-07-09 00:00:00

  • Rare Functional Variants in Complement Genes and Anti-FH Autoantibodies-Associated aHUS.

    abstract::Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and renal failure. It is caused by genetic or acquired defects of the complement alternative pathway. Factor H autoantibodies (anti-FHs) have been reported in 10% of aHUS patients and are as...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2019.00853

    authors: Valoti E,Alberti M,Iatropoulos P,Piras R,Mele C,Breno M,Cremaschi A,Bresin E,Donadelli R,Alizzi S,Amoroso A,Benigni A,Remuzzi G,Noris M

    更新日期:2019-05-01 00:00:00

  • Highlight of Immune Pathogenic Response and Hematopathologic Effect in SARS-CoV, MERS-CoV, and SARS-Cov-2 Infection.

    abstract::A sudden outbreak of COVID-19 caused by a novel coronavirus, SARS-CoV-2, in Wuhan, China in December 2019 quickly grew into a global pandemic, putting at risk not only the global healthcare system, but also the world economy. As the disease continues to spread rapidly, the development of prophylactic and therapeutic a...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2020.01022

    authors: Liang Y,Wang ML,Chien CS,Yarmishyn AA,Yang YP,Lai WY,Luo YH,Lin YT,Chen YJ,Chang PC,Chiou SH

    更新日期:2020-05-12 00:00:00

  • Conventional Dendritic Cells and Slan+ Monocytes During HIV-2 Infection.

    abstract::HIV-2 infection is characterized by low viremia and slow disease progression as compared to HIV-1 infection. Circulating CD14++CD16+ monocytes were found to accumulate and CD11c+ conventional dendritic cells (cDC) to be depleted in a Portuguese cohort of people living with HIV-2 (PLWHIV-2), compared to blood bank heal...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.01658

    authors: Iannetta M,Isnard S,Manuzak J,Guillerme JB,Notin M,Bailly K,Andrieu M,Amraoui S,Vimeux L,Figueiredo S,Charmeteau-de Muylder B,Vaton L,Hatton EX,Samri A,Autran B,Thiébaut R,Chaghil N,Glohi D,Charpentier C,Descamps D

    更新日期:2020-08-13 00:00:00

  • Investigating Immunization With Nucleotide Enzymes of Schistosoma mansoni: Nucleoside Diphosphate Kinase and Adenylosuccinate Lyase as New Antigenic Targets Against Schistosomiasis.

    abstract::Schistosomiasis, caused by Schistosoma mansoni trematode worm, affects more than 1.5 million people in Brazil. The current treatment consists in the administration of Praziquantel, the only medicine used for treatment for more than 40 years. Some of the limitations of this drug consist in its inactivity against schist...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2020.569988

    authors: Cagnazzo TDO,Nogueira CT,de Castro CA,Neris DM,Fattori ACM,Correia RO,Albuquerque YR,Fragelli BDL,Mendes TMF,Allegretti SM,Soares EG,Romanello L,Torini JR,Pereira HD,Anibal FF

    更新日期:2020-09-23 00:00:00

  • Hypothermia Promotes Interleukin-22 Expression and Fine-Tunes Its Biological Activity.

    abstract::Disturbed homeostasis as a result of tissue stress can provoke leukocyte responses enabling recovery. Since mild hypothermia displays specific clinically relevant tissue-protective properties and interleukin (IL)-22 promotes healing at host/environment interfaces, effects of lowered ambient temperature on IL-22 were s...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2017.00742

    authors: Chichelnitskiy E,Himmelseher B,Bachmann M,Pfeilschifter J,Mühl H

    更新日期:2017-06-29 00:00:00

  • Inflammation and Lymphatic Function.

    abstract::The lymphatic vasculature plays a crucial role in regulating the inflammatory response by influencing drainage of extravasated fluid, inflammatory mediators, and leukocytes. Lymphatic vessels undergo pronounced enlargement in inflamed tissue and display increased leakiness, indicating reduced functionality. Interferin...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章,评审

    doi:10.3389/fimmu.2019.00308

    authors: Schwager S,Detmar M

    更新日期:2019-02-26 00:00:00

  • Role of female sex hormones, estradiol and progesterone, in mast cell behavior.

    abstract::Female sex hormones have long been suspected to have an effect on mast cell (MC) behavior. This assumption is based on the expression of hormone receptors in MCs as well as on the fact that many MC-related pathophysiological alterations have a different prevalence in females than in males. Further, serum IgE levels ar...

    journal_title:Frontiers in immunology

    pub_type: 杂志文章

    doi:10.3389/fimmu.2012.00169

    authors: Zierau O,Zenclussen AC,Jensen F

    更新日期:2012-06-19 00:00:00