Browse
Submit Data
Databases
API
Help

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The yin and yang functions of extracellular ATP and adenosine in tumor immunity.

ABSTRACT: Extracellular adenosine triphosphate (eATP) and its main metabolite adenosine (ADO) constitute an intrinsic part of immunological network in tumor immunity. The concentrations of eATP and ADO in tumor microenvironment (TME) are controlled by ectonucleotidases, such as CD39 and CD73, the major ecto-enzymes expressed on immune cells, endothelial cells and cancer cells. Once accumulated in TME, eATP boosts antitumor immune responses, while ADO attenuates immunity against tumors. eATP and ADO, like yin and yang, represent two opposite aspects from immune-activating to immune-suppressive signals. Here we reviewed the functions of eATP and ADO in tumor immunity and attempt to block eATP hydrolysis, ADO formation and their contradictory effects in tumor models, allowing the induction of effective anti-tumor immune responses in TME. These attempts documented that therapeutic approaches targeting eATP/ADO metabolism and function may be effective methods in cancer therapy.

SUBMITTER: Feng LL

PROVIDER: S-EPMC7137337 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

The yin and yang functions of extracellular ATP and adenosine in tumor immunity.

Feng Li-Li LL Cai Yi-Qing YQ Zhu Ming-Chen MC Xing Li-Jie LJ Wang Xin X

Cancer cell international 20200407

Extracellular adenosine triphosphate (eATP) and its main metabolite adenosine (ADO) constitute an intrinsic part of immunological network in tumor immunity. The concentrations of eATP and ADO in tumor microenvironment (TME) are controlled by ectonucleotidases, such as CD39 and CD73, the major ecto-enzymes expressed on immune cells, endothelial cells and cancer cells. Once accumulated in TME, eATP boosts antitumor immune responses, while ADO attenuates immunity against tumors. eATP and ADO, like ...[more]

PMID: 32280302

Similar Datasets

The yin and yang of co-inhibitory receptors: toward anti-tumor immunity without autoimmunity.

Project description:Co-inhibitory receptors are important regulators of T-cell function that define the balance between tolerance and autoimmunity. The immune regulatory function of co-inhibitory receptors, including CTLA-4, PD-1, TIM-3, TIGIT, and LAG-3, was first discovered in the setting of autoimmune disease models, in which their blockade or deficiency resulted in induction or exacerbation of the disease. Later on, co-inhibitory receptors on lymphocytes have also been found to influence outcomes in tumor and chronic viral infection settings. These receptors suppress T-cell function in the tumor microenvironment (TME), thereby making the T cells dysfunctional. Based on this observation, blockade of co-inhibitory receptors (also known as checkpoint molecules) has emerged as a successful treatment option for a number of human cancers. However, severe autoimmune-like side effects limit the use of therapeutics that block individual or combinations of co-inhibitory receptors for cancer treatment. In this review we provide an overview of the role of co-inhibitory receptors in autoimmunity and anti-tumor immunity. We then discuss current approaches and future directions to leverage our knowledge of co-inhibitory receptors to target them in tumor immunity without inducing autoimmunity.

| S-EPMC7118128 | biostudies-literature

The Yin and Yang of microRNAs: leukemia and immunity.

Project description:Yin and Yang are two complementary forces that together describe the nature of real-world elements. Yin is the dark side; Yang is the light side. We describe microRNAs having both Yin and Yang characteristics because they can contribute to normal function (Yang) but also to autoimmunity, myeloproliferation, and cancer (Yin). We have been working on a number of microRNAs that have these dual characteristics and here we focus on two, miR-125b and miR-146a. We have concentrated on these two RNAs because we have very extensive knowledge of them, much of it from our laboratory, and also because they provide a strong contrast: the effects of overexpression of miR-125b are rapid, suggesting that it acts directly, whereas the effects of miR-146a are slow to develop, suggesting that they arise from chronic alterations in cellular behavior.

| S-EPMC3620843 | biostudies-literature

The yin-yang of long pentraxin PTX3 in inflammation and immunity.

Project description:Pentraxins are a family of multimeric proteins characterized by the presence of a pentraxin signature in their C-terminus region. Based on the primary structure, pentraxins are divided into short and long pentraxin: C-reactive protein (CRP) is the prototype of the short pentraxin subfamily while pentraxin 3 (PTX3) is the prototypic long pentraxin. Despite these two molecules exert similar fundamental actions in the regulation of innate immune and inflammatory responses, several differences exist between CRP and PTX3, including gene organization, protein oligomerization and expression pattern. The pathophysiological roles of PTX3 have been investigated using genetically modified mice since PTX3 gene organization and regulation are well conserved between mouse and human. Such in vivo studies figured out that PTX3 mainly have host-protective effects, even if it could also exert negative effects under certain pathophysiologic conditions. Here we will review the general properties of CRP and PTX3, emphasizing the differences between the two molecules and the regulatory functions exerted by PTX3 in innate immunity and inflammation.

| S-EPMC7112810 | biostudies-literature

Influenza Hemagglutinin and Neuraminidase: Yin⁻Yang Proteins Coevolving to Thwart Immunity.

Project description:Influenza A virions possess two surface glycoproteins-the hemagglutinin (HA) and neuraminidase (NA)-which exert opposite functions. HA attaches virions to cells by binding to terminal sialic acid residues on glycoproteins/glycolipids to initiate the infectious cycle, while NA cleaves terminal sialic acids, releasing virions to complete the infectious cycle. Antibodies specific for HA or NA can protect experimental animals from IAV pathogenesis and drive antigenic variation in their target epitopes that impairs vaccine effectiveness in humans. Here, we review progress in understanding HA/NA co-evolution as each acquires epistatic mutations to restore viral fitness to mutants selected in the other protein by host innate or adaptive immune pressure. We also discuss recent exciting findings that antibodies to HA can function in vivo by blocking NA enzyme activity to prevent nascent virion release and enhance Fc receptor-based activation of innate immune cells.

| S-EPMC6520700 | biostudies-literature

A possible representation of Yin Yang five elements (Yin Yang Wu Xing): Hypothesis of Dual Five-Body-Coordination.

Project description:BackgroundThe idea of Yin Yang Wu Xing, traditionally adopted and practiced in East-Asian medicine, has not been incorporated into the theoretical framework of modern medicine. It is therefore desired to show that Yin Yang Wu Xing is a manifestation of a higher-level faculty of cooperating system, thus making it suitable for a modern frame of thought.MethodsA higher-level faculty of the cooperating system is formulated in the scheme of Dual Five-Body Coordination. The stability of this scheme is examined mathematically and the feasibility of its physical realization is estimated.ResultsThe Dual Five-Body Coordination scheme, which overlaps substantially with the conceptual structure of Yin Yang Wu Xing, is stable and has survival merit. An imaginable conjecture based on physical reality confirms its physical feasibility.ConclusionThe Dual Five-Body Coordination scheme has potential utilization in various fields including biology and sociology. Once the theoretical framework is solidified, the Dual Five-Body Coordination scheme can be readily applied in practical research in modern medicine.

| S-EPMC7473878 | biostudies-literature

The oncogenic role of Yin Yang 1.

Project description:Yin Yang 1 (YY1) is a transcription factor with diverse and complex biological functions. YY1 either activates or represses gene transcription, depending on the stimuli received by the cells and its association with other cellular factors. Since its discovery, a biological role for YY1 in tumor development and progression has been suggested because of its regulatory activities toward multiple cancer-related proteins and signaling pathways and its overexpression in most cancers. In this review, we primarily focus on YY1 studies in cancer research, including the regulation of YY1 as a transcription factor, its activities independent of its DNA binding ability, the functions of its associated proteins, and mechanisms regulating YY1 expression and activities. We also discuss the correlation of YY1 expression with clinical outcomes of cancer patients and its target potential in cancer therapy. Although there is not a complete consensus about the role of YY1 in cancers based on its activities of regulating oncogene and tumor suppressor expression, most of the currently available evidence supports a proliferative or oncogenic role of YY1 in tumorigenesis.

| S-EPMC3386643 | biostudies-literature

Targeting CD39 in Cancer Reveals an Extracellular ATP- and Inflammasome-Driven Tumor Immunity.

Project description:We explored the mechanism of action of CD39 antibodies that inhibit ectoenzyme CD39 conversion of extracellular ATP (eATP) to AMP and thus potentially augment eATP-P2-mediated proinflammatory responses. Using syngeneic and humanized tumor models, we contrast the potency and mechanism of anti-CD39 mAbs with other agents targeting the adenosinergic pathway. We demonstrate the critical importance of an eATP-P2X7-ASC-NALP3-inflammasome-IL18 pathway in the antitumor activity mediated by CD39 enzyme blockade, rather than simply reducing adenosine as mechanism of action. Efficacy of anti-CD39 activity was underpinned by CD39 and P2X7 coexpression on intratumor myeloid subsets, an early signature of macrophage depletion, and active IL18 release that facilitated the significant expansion of intratumor effector T cells. More importantly, anti-CD39 facilitated infiltration into T cell-poor tumors and rescued anti-PD-1 resistance. Anti-human CD39 enhanced human T-cell proliferation and Th1 cytokine production and suppressed human B-cell lymphoma in the context of autologous Epstein-Barr virus-specific T-cell transfer. SIGNIFICANCE: Overall, these data describe a potent and novel mechanism of action of antibodies that block mouse or human CD39, triggering an eATP-P2X7-inflammasome-IL18 axis that reduces intratumor macrophage number, enhances intratumor T-cell effector function, overcomes anti-PD-1 resistance, and potentially enhances the efficacy of adoptive T-cell transfer.This article is highlighted in the In This Issue feature, p. 1631.

| S-EPMC6891207 | biostudies-literature

Yin Yang 1 promotes mTORC2-mediated AKT phosphorylation.

Project description:Yin Yang 1 (YY1) regulates both gene expression and protein modifications, and has shown a proliferative role in cancers. In this study, we demonstrate that YY1 promotes AKT phosphorylation at S473, a marker of AKT activation. YY1 expression positively correlated with AKT(S473) phosphorylation in a tissue microarray and cultured cells of breast cancer, but negatively associated with the distant metastasis-free survival of 166 breast cancer patients. YY1 promotes AKT phosphorylation at S473 through direct interaction with AKT, and the AKT-binding site is mapped to the residues G201-S226 on YY1. These residues are also involved in YY1 interaction with Mdm2, Ezh2, and E1A, and thus are designated as the oncogene protein binding (OPB) domain. YY1-promoted AKT phosphorylation relies on the OPB domain but is independent of either transcriptional activity of YY1 or the activity of phosphoinositide-3-kinases. We also determine that YY1-promoted mTORC2 access to AKT leads to its phosphorylation at S473. Importantly, a peptide based on the OPB domain blocks YY1 interaction with AKT and reduces AKT phosphorylation and cell proliferation. Thus, we demonstrate for the first time that YY1 promotes mTORC2-mediated AKT activation and disrupting YY1-AKT interaction by OPB domain-based peptide may represent a potential strategy for cancer therapy.

| S-EPMC5007621 | biostudies-literature

IL-17 Signaling: The Yin and the Yang.

Project description:Interleukin (IL)-17 is the founding member of a novel family of inflammatory cytokines. While the proinflammatory properties of IL-17 are key to its host-protective capacity, unrestrained IL-17 signaling is associated with immunopathology, autoimmune disease, and cancer progression. In this review we discuss both the activators and the inhibitors of IL-17 signal transduction, and also the physiological implications of these events. We highlight the surprisingly diverse means by which these regulators control expression of IL-17-dependent inflammatory genes, as well as the major target cells that respond to IL-17 signaling.

| S-EPMC5411326 | biostudies-literature

The Yin and Yang of Discoidin Domain Receptors (DDRs): Implications in Tumor Growth and Metastasis Development.

Project description:The tumor microenvironment is a complex structure composed of the extracellular matrix (ECM) and nontumoral cells (notably cancer-associated fibroblasts (CAFs) and immune cells). Collagens are the main components of the ECM and they are extensively remodeled during tumor progression. Some collagens are ligands for the discoidin domain receptor tyrosine kinases, DDR1 and DDR2. DDRs are involved in different stages of tumor development and metastasis formation. In this review, we present the different roles of DDRs in these processes and discuss controversial findings. We conclude by describing emerging DDR inhibitory strategies, which could be used as new alternatives for the treatment of patients.

| S-EPMC8038660 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data