• In recent years, numerous studies have revealed that XBP1 plays a vital role in bone metabolism, including osteoclast and osteoblast development, as well as in regulating immune cell differentiation that affects the immune microenvironment of bone remodeling. (bvsalud.org)
  • In this review, we highlight the regulatory mechanisms of XBP1 on osteoclasts and osteoblasts, how XBP1 affects the immune microenvironment of bone remodeling by influencing the differentiation of immune cells, and predict the possible future research directions of XBP1 to provide new insights for the treatment of bone-related metabolic diseases. (bvsalud.org)
  • Tumors exhibit significant myeloid cell infiltrates, which are actively recruited to the tumor microenvironment. (hindawi.com)
  • Finally, we will comment on the mechanisms regulating myeloid cell recruitment to the tumor microenvironment and on the potential of myeloid cells as new targets for cancer therapy. (hindawi.com)
  • Notch signaling cascades crosstalk with fibroblast growth factor and WNT signaling cascades in the tumor microenvironment to maintain cancer stem cells and remodel the tumor microenvironment. (spandidos-publications.com)
  • Germline mutations in the NOTCH1 , NOTCH2 and NOTCH3 genes cause Adams-Oliver syndrome, Alagille syndrome and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, respectively ( 4 ), and DLL4-NOTCH3 signaling in human vascular organoids induces basement membrane thickening and drives vasculopathy in the diabetic microenvironment ( 5 ). (spandidos-publications.com)
  • Conclusion: Our study suggests that the RANKL/RANK pathway contributes to the development and maintenance of the immunosuppressive tumor microenvironment and denosumab may be a promising adjuvant therapy targeting TAMs in cancer of apocrine origin. (iiarjournals.org)
  • Of these, tumor-associated macrophages (TAMs) and regulatory T-cells (Tregs) create an immunosuppressive microenvironment through various pathways. (iiarjournals.org)
  • For example, Paget's cells release soluble receptor activator of nuclear factor kappa-B ligand (sRANKL) into the tumor microenvironment, stimulating RANK + TAMs to produce CCL17, which recruits Tregs into the lesional skin of patients with extramammary Paget's disease (EMPD) ( 11 , 17 ). (iiarjournals.org)
  • Accordingly, investigating the characteristics of cancer-related factors is important to determine the immunological background of the tumor microenvironment in each type of skin cancer. (iiarjournals.org)
  • In the bone microenvironment, breast cancer cells produce osteoclast (OC)-activating cytokines, including parathyroid hormone-related protein (PTH-rP), prostaglandin E 2 (PEG 2 ), and interleukin-11 (IL-11) [ 5 ], which can increase expression of receptor activator of nuclear factor-κB ligand (RANKL) by osteoblasts (OBs). (oncotarget.com)
  • It is safe to assume that the phenotype and functions of non-tumor cells such as endothelial cells, fibroblasts or macrophages residing in the microenvironment of primary tumors differ from those of similar non-tumor cells residing in metastatic microenvironments. (eurekaselect.com)
  • Tumor-microenvironment interactions should, thus, be studied in the context of the site. (eurekaselect.com)
  • This short review summarizes state of the art with respect to interactions between the brain microenvironment with brain-metastasizing tumor cells. (eurekaselect.com)
  • γδ T cells recruited into the tumor microenvironment can act as effector cells to mediate cancer immune surveillance. (explorationpub.com)
  • Therefore, an in-depth understanding of γδ T cells that play conflicting roles in the tumor microenvironment is necessary. (explorationpub.com)
  • This receptor has been shown to activate NF-κB and MAPK8/JNK, and induce cell apoptosis. (wikipedia.org)
  • DR6 induces apoptosis when it is over expressed, however the manner in which the death signal is intracellularly transduced is currently unknown. (wikipedia.org)
  • Circulating osteoprotegerin (OPG), a member of the receptor activator of nuclear factor kappa-B (RANK) axis, may influence breast cancer risk via its role as the decoy receptor for both the RANK ligand (RANKL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). (biomedcentral.com)
  • Transcriptomics analyses showed pathways related to TCR signaling, cytotoxicity and oxidative phosphorylation were significantly enriched in Tet lo found in both regressing and progressing tumors compared with Tet hi , whereas genes related to DNA damage, apoptosis and autophagy were downregulated. (bmj.com)
  • Depending on the cellular context, TNF can induce diverse effects such as necrosis, apoptosis, differentiation, angiogenesis, cell migration and immune cell activation. (eurekaselect.com)
  • As a signaling molecule, LT-α is involved in the regulation of cell survival, proliferation , differentiation , and apoptosis . (wikidoc.org)
  • Cell death occurs under physiological and pathological conditions and mediates through three pathways as follows: apoptosis, autophagic cell death, and necrosis. (biomedcentral.com)
  • In contrast to necrosis (murdered cells), in apoptosis (commit suicide) and autophagy process, cytoplasmic membranes are maintained and cell body is completely removed without any inflammation. (biomedcentral.com)
  • However, if phagocytosis of the cell does not occur at the final stage of apoptosis or autophagic process, the cells are removed through secondary necrosis [ 12 ]. (biomedcentral.com)
  • Selective AHR deletion in eosinophils depleted Clec4a4+ eosinophils, augmented innate lymphocytes producing type 2 cytokines, and enhanced helminth clearance. (stanford.edu)
  • First described in 1975, NK cells were initially identified as a distinct sub-population of lymphocytes by their capacity to spontaneously lyse tumor cells ( 1 ). (frontiersin.org)
  • Tumor-infiltrating lymphocytes are related to positive clinical prognoses in numerous cancer types. (cancer-genetics.org)
  • Lymphotoxin alpha, a member of the tumor necrosis factor family , is a cytokine produced by lymphocytes . (wikidoc.org)
  • Human derived T lymphocytes engineered to express chimeric antigen receptors, which are expanded in vitro culture and then infused into patients exerting robust cytotoxicity after tumor antigen recognition and subsequent activation. (biomedcentral.com)
  • Activated γδ T cells exhibit strong cytotoxic activity and cytokine secretion functions and are effective antitumor lymphocytes with simple and direct recognition modes and rapid responses. (explorationpub.com)
  • NK1.1 (Killer cell lectin-like receptor subfamily B, member 1, KLRB1, NKR-P1A, CD161, cluster of differentiation 161), refers to Natural Killer (NK) cells, lymphocytes that mediate cytotoxicity and secrete cytokines after immune stimulation. (thermofisher.com)
  • Inflammatory dysregulation resulting from each organ failure results in rising levels of circulating chemokines, cytokines and activated lymphocytes [ 17 ]. (biomedcentral.com)
  • As we previously reported, receptor activator of nuclear factor kappa-B (RANK) ligand (RANKL)/RANK signaling on M2 macrophages promotes the production of chemokines and proinflammatory cytokines to maintain the immunosuppressive tumor environment of extramammary Paget's disease (EMPD). (iiarjournals.org)
  • Its surface mesothelium and submesothelial stroma and structure pose no substantial barriers to inflammatory modulatory cytokines, chemokines and other molecules produced by the tumor or its metastasis, at least to a depth of approximately 1 mm [ 2 ]. (biomedcentral.com)
  • Pancreatic acinar cell injury triggers the synthesis and release of pro-inflammatory cytokines and chemokines (32, 36, 39, 41, 82). (pancreapedia.org)
  • This review aims to describe the roles of key cytokines and chemokines in commonly used experimental models of pancreatitis and how the cytokine profile is affected by the choice of a specific model. (pancreapedia.org)
  • Another mechanism whereby injured pancreatic acinar cells trigger the inflammatory response is through synthesis and release of cytokines (36) and chemokines (11), and upregulation of adhesion molecules such as the intercellular adhesion molecule-1 (ICAM-1) (136), which together promote neutrophil and monocyte infiltration (27, 71) and exacerbate tissue injury (10, 27, 37). (pancreapedia.org)
  • Chemokines (chemotactic cytokines) are positively charged polypeptides with highly conserved cysteine (C) residues within the N-terminal sequence, classifying them as 'C', 'CC', 'CXC' or 'CX3C' types (102, 143). (pancreapedia.org)
  • In the context of AP, the most extensively investigated chemokines are CC-ligand 2 (CCL2, also known as monocyte chemoattractant protein-1 or MCP-1), CXC-ligand 1 (CXCL1, also known as cytokine-induced neutrophil chemoattractant or CINC in rat and keratinocyte cytokine or KC in mouse), and CXC-ligand 2 (CXCL2, also known as macrophage inflammatory protein 2-alpha or MIP2a). (pancreapedia.org)
  • After a stroke, a cascade of molecules such as damage-associated molecular patterns, cytokines, chemokines, complement factors, prostaglandins, and transforming growth factor beta are released to fix the cerebral outcome. (biomedcentral.com)
  • Tumor cells can induce, through exposition of amyloid precursor protein (APP), DR6-mediated endothelial cell necroptosis allowing tumors metastasis. (wikipedia.org)
  • Myeloid cells are a heterogeneous population of bone marrow-derived cells that play a critical role during growth and metastasis of malignant tumors. (hindawi.com)
  • Myeloid cells promote tumor growth by stimulating tumor angiogenesis, suppressing tumor immunity, and promoting metastasis to distinct sites. (hindawi.com)
  • Angiogenesis, the growth of new blood vessels, occurs at different stages during embryonic development, physiological processes such as wound healing and reproduction, and numerous diseases, including inflammation, tumor progression, and metastasis [ 1 ]. (hindawi.com)
  • This suggested that EPCs are able to differentiate into endothelial cells and that such cells are incorporated into sites of active angiogenesis including ischemia, tumor angiogenesis, and metastasis in adult organisms [ 16 , 17 ]. (hindawi.com)
  • More recent data show that OPG is also produced in breast tumor cells, and that it can promote tumor growth and metastasis [ 5 , 6 ]. (biomedcentral.com)
  • Bone is a unique environment storing a variety of growth factors, and is one of the most common target sites for distant metastasis of breast cancer [ 1 ]. (oncotarget.com)
  • [3] [6] However, mice with overexpression of LT-α or LT-β showed increased tumor growth and metastasis in several models of cancer. (wikidoc.org)
  • Knockout studies in mice suggested that this gene plays a role in T helper cell activation, and may be involved in inflammation and immune regulation. (wikipedia.org)
  • Inflammation induced by wear particles derived from prosthetic biomaterials is a major cause of osteolysis. (bvsalud.org)
  • It is presently unknown whether peroxisome proliferator-activated receptor (PPAR) β/δ activation prevents inflammation in adipocytes. (diabetesjournals.org)
  • In addition, the effects of macrophages in the occurrence and development of inflammatory bowel disease (IBD), and their role in inducing fibrosis, activating T cells, reducing colitis, and treating intestinal inflammation were also reviewed in this paper. (frontiersin.org)
  • Pentraxin 3 (PTX3), a modulator of tumor-associated inflammation, is known to be positively correlated with tumor grade and severity of malignancies, but its exact role remains unclear. (oncotarget.com)
  • During the process of airway inflammation, complex interactions of innate and adaptive immune cells as well as structural cells and their cytokines have many important roles. (cdc.gov)
  • Interleukin (IL)-9-producing subset called Th9 cell, Th22 cells which primarily secrete IL-22, IL-13 and tumor necrosis factor- and Th25 cells via producing IL-25 are believed to be important for initiating allergic reactions and developing airway inflammation. (cdc.gov)
  • 4] After allergen exposure, that produced exceptionally large quantities of airway inflammation is orchestrated mainly by cytokine IL-9. (cdc.gov)
  • Tumor Necrosis Factor (TNF) is a pleiotropic cytokine with a central role in immune homeostasis, inflammation and host defence. (eurekaselect.com)
  • Categorizing genes on the basis of annotated gene function led to our observing that genes associated with inflammation were overexpressed in non-tumor bearing peritoneum of patients with ovarian cancer as compared with the peritoneum of patients with benign ovarian tumors. (biomedcentral.com)
  • A Deficiency in the Cytokine TNFSF14/LIGHT Limits Inflammation and Remodeling in Murine Eosinophilic Esophagitis. (ucsd.edu)
  • The Role of Cytokines and Inflammation in the Genesis of Experimental Pancreatitis. (pancreapedia.org)
  • Inflammation is either self-limiting or self-perpetuating resulting in significant organ necrosis. (pancreapedia.org)
  • NK cell activation and the triggering of effector functions is governed by a complex set of activating and inhibitory receptors. (frontiersin.org)
  • Here, we review tumor-NK cell interactions, discuss the mechanisms by which NK cells generate an antitumor immune response, and discuss NK cell-based therapeutic strategies targeting activating, inhibitory, and co-stimulatory receptors. (frontiersin.org)
  • However, CD56 dim NK cells can produce cytokines, specifically IFN-γ, after cell triggering via NKp46 of NKp30 activating receptors or after stimulation with combinations of IL-2, IL-12, and IL-15 ( 7 ). (frontiersin.org)
  • NOTCH1, NOTCH2, NOTCH3 and NOTCH4 are transmembrane receptors that transduce juxtacrine signals of the delta‑like canonical Notch ligand (DLL)1, DLL3, DLL4, jagged canonical Notch ligand (JAG)1 and JAG2. (spandidos-publications.com)
  • Small‑molecule γ‑secretase inhibitors (AL101, MRK‑560, nirogacestat and others) and antibody‑based biologics targeting Notch ligands or receptors [ABT‑165, AMG 119, rovalpituzumab tesirine (Rova‑T) and others] have been developed as investigational drugs. (spandidos-publications.com)
  • This cytokine is a ligand for receptors TNFRSF13B /TACI, TNFRSF17 /BCMA, and TNFRSF13C /BAFF-R. This cytokine is expressed in B cell lineage cells, and acts as a potent B cell activator. (wikidoc.org)
  • [4] BAFF is the natural ligand of three unusual tumor necrosis factor receptors named BAFF-R (BR3), TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor), and BCMA (B-cell maturation antigen), all of which have differing binding affinities for it. (wikidoc.org)
  • All these ligands act as homotrimers (i.e. three of the same molecule) interacting with homotrimeric receptors, [6] although BAFF has been known to be active as either a hetero- or homotrimer (can aggregate into 60-mer depending on the primary structure of the protein). (wikidoc.org)
  • As a member of the TNF family , LT-α binds to various receptors and activates the NF-κB pathway , thus promoting immune regulation through the innate immune response. (wikidoc.org)
  • Formation of LT-α 1 -β 2 complex enables binding to LT-β receptors and subsequent activation of signaling pathways. (wikidoc.org)
  • Activation of LT-β receptors is capable of inducing cell death of cancerous cells and suppressing tumor growth. (wikidoc.org)
  • Aiming at wear particle-induced periprosthetic aseptic osteolysis, this review separately discusses the molecular mechanism of regulation of ROS formation and inflammatory response through intervention of macrophage/osteoclast RANKL-MAPKs-NF-κB pathway. (bvsalud.org)
  • In vivo, we discovered that osteoclast-specific knockout of suppressed RANKL-induced osteoclastogenesis, bone resorption function, and osteoclast-specific gene expression (Ctsk, TRAP, MMP-9, NFATc1). (bvsalud.org)
  • Western blot analyses of RANKL-induced signaling pathways showed that conditional knockout of PDK1 in osteoclasts inhibited the early nuclear factor κB (NF-κB) activation, which consequently suppressed the downstream induction of NFATc1. (bvsalud.org)
  • Homeostatic osteoclastogenesis is effectively induced by RANKL (Receptor activator of nuclear factor kappa-B ligand). (frontiersin.org)
  • TNF and RANKL are members of the TNF superfamily. (frontiersin.org)
  • Osteoclast differentiation is induced by the master osteoclastogenic factor, RANKL, which acts in concert with M-CSF and ITAM-mediated co-stimulatory signaling. (frontiersin.org)
  • Understanding the mechanistic difference between RANKL-mediated physiological and TNF-mediated inflammatory osteoclastogenesis, and especially TNF-induced intrinsic inhibitory mechanisms, will strengthen the development of therapeutic approaches to treat pathological bone destruction in disease settings and prevent negative side effects on bone remodeling and immunity. (frontiersin.org)
  • Since EMPD is a skin adenocarcinoma of apocrine gland origin that expresses high levels of RANKL and matrix metalloproteinase (MMP) 7, and EMPD is associated with the presence of RANK + M2 macrophages, we hypothesized that tumor-associated macrophages (TAMs) in adenocarcinomas such as PCAC might also express RANKL and MMP7. (iiarjournals.org)
  • Bone homeostasis is maintained by the interplay between the receptor activator of nuclear factor kappa-B (RANK), its soluble activation ligand (RANKL), and OPG. (biomedcentral.com)
  • OPG binds RANKL as a decoy receptor, inhibiting the activation of RANK by RANKL and preventing the differentiation of bone marrow precursor (monocyte/macrophage) cells to osteoclasts - cells that are central in the process of bone resorption [ 2 ]. (biomedcentral.com)
  • RANKL is a potent stimulator of OC differentiation and OC activity, and leads to excess bone destruction [ 5 , 6 ]. (oncotarget.com)
  • It is now known that new blood vessels originate from preexisting vessels by activation, proliferation and migration of endothelial cells through a process named "angiogenesis" [ 4 ]. (hindawi.com)
  • Specific growth factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), stimulate the proliferation and migration of naturally quiescent endothelial cells, resulting in the formation of new vessel structures during embryonic development and tumor growth [ 7 ]. (hindawi.com)
  • PDF) Kraan J, van den Broek P, Verhoef C, Grunhagen DJ, Taal W, Gratama JW, Sleijfer SEndothelial CD276 (B7-H3) expression is increased in human malignancies and distinguishes between normal and tumour-derived circulating endothelial cells. (researchgate.net)
  • METHODS: In our study, we used a receptor activator of nuclear factor-kappa B (RANK) promoter-driven Cre-LoxP system to conditionally delete the PDK1 gene in osteoclasts in mice. (bvsalud.org)
  • Several antigens have been used as targets for CAR-T cell therapy against MM, including B cell maturation antigen (BCMA), CD19, CD138, signaling lymphocytic activation molecule 7 (SLAM7), and immunoglobulin light chains. (biomedcentral.com)
  • Two main advantages of BCMA as an antigen for CAR-T therapy are the potential reduction of on-target/off-tumor toxicity and the lack of antigen-dependent reduction in CAR-T cell expansion [ 16 ]. (biomedcentral.com)
  • The expression of B7 proteins on an antigen-presenting cell is induced by pathogens during the innate response to an infection. (nih.gov)
  • Methods: Identification of tumour-associated endothelial markers (TEM) by comparing antigen expression on normal vs t-CEC and assess the presence of t-CEC in peripheral blood of cancer patients by incorporating TEM in our novel flow cytometry-based CEC detection assay. (researchgate.net)
  • However, relapse of primary disease remains a major obstacle after CAR T cells therapy, and the majority of relapses present a tumor phenotype with retention of target antigen (antigen-positive relapse), which highly correlate with poor CAR T cells persistence. (biomedcentral.com)
  • Cell-cell interactions between antigen presenting cells and T cells provide bidirectional signaling that is critical for the activation, maturation, and effector function of both cell types. (biomedcentral.com)
  • RESEARCH DESIGN AND METHODS AND RESULTS- First, we examined whether the PPARβ/δ agonist GW501516 prevents lipopolysaccharide (LPS)-induced cytokine production in differentiated 3T3-L1 adipocytes. (diabetesjournals.org)
  • 3,3′-diindolylmethane (DIM)-a natural compound produced from indole-3-carbinol, found in cruciferous vegetables-enhances glucose uptake by increasing the activation of the insulin signaling pathway in 3T3-L1 adipocytes. (researchgate.net)
  • Cytokines secreted by adipocytes, such as tumor necrosis factor-α, transforming growth factor-β, and interleukin-6, are implicated in NAFLD. (wjgnet.com)
  • OBJECTIVE- We identified lipocalin 2 ( Lcn2 ) as a gene induced by dexamethasone and tumor necrosis factor-α in cultured adipocytes. (diabetesjournals.org)
  • Genotoxic damage causes robust alterations to pathways associated with B cell activation and increased proliferation, suggesting that genotoxic damage initiates not only the normal B cell maturation processes but also mimics activated B cell response to antigenic agents. (biomedcentral.com)
  • However, as tumors progress, cancerous cells develop immunosuppressive mechanisms that circumvent NK cell-mediated killing, allowing for tumor escape and proliferation. (frontiersin.org)
  • And TGF-β, just going back to that, is specific to cellular function in terms of cell growth, proliferation, differentiation. (chiroeco.com)
  • It has been also shown to play an important role in the proliferation and differentiation of B cells. (wikidoc.org)
  • [5] TACI binds worst since its affinity is higher for a protein similar to BAFF, called a proliferation-inducing ligand (APRIL). (wikidoc.org)
  • [15] Activation of signaling pathways such as NF-κB ultimately leads to various cellular fates, including cell proliferation and cell death. (wikidoc.org)
  • BCMA, a member of the tumor necrosis factor (TNF) superfamily, is exclusively expressed in a subpopulation of B cells, normal plasma cells, and malignant plasma cells. (biomedcentral.com)
  • Moreover, BCMA plays an essential role in regulating B cell maturation and differentiation into plasma cells. (biomedcentral.com)
  • As the only bone resorbing cells in vivo, osteoclasts play important roles in cancer-induced osteolysis. (bvsalud.org)
  • Bone marrow-derived macrophage cells (BMMs) were extracted and induced to differentiate osteoclasts in vitro to explore the role of PDK1 in osteoclasts. (bvsalud.org)
  • Induces osteoclastogenesis by activating multiple signaling pathways in osteoclast precursor cells, chief among which is induction of long lasting oscillations in the intracellular concentration of Ca (2+) resulting in the activation of NFATC1, which translocates to the nucleus and induces osteoclast-specific gene transcription to allow differentiation of osteoclasts. (cusabio.com)
  • Comparing these transcriptional responses provides a greater understanding of the mechanisms cells use in the differentiation between types of DNA damage and the potential consequences of different sources of damage. (biomedcentral.com)
  • Remarkably, Clec4a4+ eosinophils were instructed by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that imprints many gut immune cells. (stanford.edu)
  • There is compelling clinical and experimental evidence to suggest that natural killer (NK) cells play a critical role in the recognition and eradication of tumors. (frontiersin.org)
  • Nascent transformed cells elicit NK cell activation and are eliminated. (frontiersin.org)
  • Therapeutic intervention aims to reverse tumor-induced NK cell suppression and sustain NK cells' tumorlytic capacities. (frontiersin.org)
  • instead of targeting tumor cells, the goal of immunotherapy is to augment and expand the immune system's intrinsic antitumor response. (frontiersin.org)
  • However, a class of important immune-modulators is conspicuously absent: agents that utilize the power of innate immune cells to eradicate tumors. (frontiersin.org)
  • NK cells are now accepted to play an important role in both the adaptive and innate immune responses that govern infection, autoimmunity, and tumor immunosurveillance ( 2 , 3 ). (frontiersin.org)
  • In this review, we discuss the role of myeloid cells in promoting tumor angiogenesis. (hindawi.com)
  • Importantly, during tumor progression, myeloid cells are implicated in promoting tumor angiogenesis, causing resistance against antiangiogenic therapies in cancer, and suppressing the immune response during cancer [ 3 - 5 ]. (hindawi.com)
  • In 1971, Dr. Judah Folkman observed that neovascularization occurs around tumors and proposed that new blood vessel growth is necessary to supply nutrients and oxygen to tumor cells during exponential tumor growth [ 6 ]. (hindawi.com)
  • Although tumor cells were first thought to drive the cellular events underpinning tumor angiogenesis and growth, considerable evidence has now emerged for the central role of tumor infiltrating myeloid cells such as monocytes, macrophages, and neutrophils in this phenomenon [ 8 - 12 ]. (hindawi.com)
  • Subsequent studies described a VEGFR2 and AC133 expressing subpopulation of these CD34 positive circulating cells that could form endothelial colonies in vitro [ 14 , 15 ]. (hindawi.com)
  • The basic and common immunologic defect in common variable immunodeficiency is a failure of B-lymphocyte differentiation into plasma cells that produce the various immunoglobulin (Ig) isotypes. (medscape.com)
  • On the other hand, phagosomes are formed when the pathogen is engulfed by macrophages and fuse with lysosomes to release enzymes and toxic substances, resulting in killing or having cytotoxic effects on bacteria and tumor cells. (frontiersin.org)
  • Previous studies have found that DIM can improve type 2 diabetes by enhancing glucose uptake through the activation of insulin signaling in 3T3-L1 cells, and by lowering the plasma glucose levels in high-fat-diet-fed obese mice [13, 14]. (researchgate.net)
  • Immunohistochemical staining of MMP1 and MMP25 as well as chemokine (C-C motif) ligand (CCL) 5 in the lesional skin from five patients with PCAC showed a substantial number of MMP1-bearing cells and MMP25-bearing cells, as well as CCL5-producing cells, that were distributed in the lesional skin. (iiarjournals.org)
  • Among immune cells, Foxp3 + regulatory T cells (Treg cells) are potent inhibitors of cancer immunity, and their presence within solid tumors is generally associated with a poor prognosis. (mdpi.com)
  • NK cells were subsequently analyzed for changes in surface marker expression, cytokine production, gene expression changes, and cytotoxic function using flow cytometry, ELISA, qRT-PCR, and cell-mediated cytotoxicity assay, respectively. (biomedcentral.com)
  • Based on effector function, NK cells are divided into two major subsets: more cytotoxic NK cells (CD56 dim CD16 + ) and more cytokine-secreting NK cells (CD56 bright CD16 dim/- ) [ 5 ]. (biomedcentral.com)
  • NKG2D is an activating NK cell surface receptor that recognizes ligands, such as MHC class I polypeptide-related sequence (MIC) A and B and UL16-binding proteins (ULPBs), displayed on the surfaces of stressed cells, thereby preventing non-specific killing by bringing NK cells into close proximity with their targets [ 7 ]. (biomedcentral.com)
  • Further insights on the roles of CD8 + specificities and TCR avidity of naturally arising tumor-specific T cells, where both high and low avidity T cells recognizing the same peptide-major histocompatibility complex (pMHC) coexist in the same tumor, are crucial for understanding T cell exhaustion and resistance to PD-1 immunotherapy. (bmj.com)
  • Tetramer staining was performed to determine the frequency and avidity of CD8 + T cells targeting the tumor-specific epitope GSW11 and confirmed with tetramer competition assays. (bmj.com)
  • High avidity T cells (Tet hi ), if present, were only found in progressing PD-1 refractory tumors. (bmj.com)
  • T helper (Th) 2 cells, which recruit and accumulate in the lungs and produce a range of different effector cytokines. (cdc.gov)
  • However, more recent studies have revealed the potential collaboration of other helper T cells and their cytokines in this process. (cdc.gov)
  • The aim of this review is to summarize the current knowledge about the possible roles of newly identified helper T cells derived cytokines (IL-9, 17, 22, 25 and IL-33) in asthma. (cdc.gov)
  • Tumor cells making up the primary tumor and those in metastatic lesions are genetically and phenotypically different. (eurekaselect.com)
  • It is therefore to be expected that the patho-biologic consequences of interactions between tumor cells and the microenvironments of the primary tumor or of the metastatic lesions will also be different. (eurekaselect.com)
  • [6] Hence depending on the context, LT-α may function to prevent growth of cancer cells or facilitate the development of tumors. (wikidoc.org)
  • As a cytotoxic protein, LT-α causes the destruction of cancerous cell lines, activates signaling pathways, and effectively kills transformed tumor cells. (wikidoc.org)
  • Therefore, study on factors and mechanisms that limit the in vivo persistence of CAR T cells is crucial for developing strategies to overcome these limitations. (biomedcentral.com)
  • In this review, we summarize the rapidly developing knowledge regarding the factors that influence CAR T cells in vivo persistence and the underlying mechanisms. (biomedcentral.com)
  • Of note, among these influence factors, CAR T cells differentiation and exhaustion are identified as the central part due to the fact that almost all factors eventually alter the state of cells differentiation and exhaustion. (biomedcentral.com)
  • Therefore, study on factors and mechanisms that limit the in vivo persistence of CAR T cells is crucial for developing strategies to reduce the probability of tumor relapse and improve the long-term disease-free survival for patients who are treated with CAR T cells. (biomedcentral.com)
  • Various factors in the process contribute to impact the in vivo persistence and durable antitumor effects of CAR T cells. (biomedcentral.com)
  • In this review, we summarize the rapidly developing knowledge regarding the influence factors and mechanisms of poor CAR T cells persistence, and also the potential strategies to overcome these limitations. (biomedcentral.com)
  • Proportions of CD68+ cells and CD3+ cells that coexpressed MO/MA differentiation factors (CD163, CCR1, CXCR8, VCAM1, and phosphorylated cytosolic phospholipase A 2 [pcPLA 2 ]), which had demonstrated expression in EOC peritoneal samples, were determined by multicolor immunofluorescence. (biomedcentral.com)
  • CD68+ MO/MA, the most commonly represented population, and CD3+ T cells were present more often in EOC than in benign pelvic tumors. (biomedcentral.com)
  • It is perhaps a paradox that the peritoneum which is organized to protect the integrity of intraabdominal organs by facilitating infiltration of inflammatory cells to sites of injury and infection, might also serve to facilitate the promotion of tumor growth and spread. (biomedcentral.com)
  • Engagement of CD40 by CD40L expressed on T cells results in the production of proinflammatory cytokines, induces T helper cell function, and promotes macrophage activation. (biomedcentral.com)
  • Its ligand, CD154 or CD40L, has a more restricted expression pattern and is found primarily on activated T cells, B cells, and platelets. (biomedcentral.com)
  • Taking advantage of the diverse γδ TCR repertoire or other ligand-receptor interactions, γδ T cells can recognize a broad spectrum of tumor-associated antigens (TAAs) in a major histocompatibility complex (MHC)-independent manner, thereby activating downstream pleiotropic effects. (explorationpub.com)
  • However, the clinical application of tumor-infiltrating γδ T cells has certain limitations. (explorationpub.com)
  • First, γδ T cells exposed to complicated cytokine networks are potentially affected by multiple inhibitory mechanisms. (explorationpub.com)
  • These cells may be a key factor ultimately mediating the deviation of the antagonistic response between tumor inhibition and tumor promotion. (explorationpub.com)
  • According to current challenges, there is a need to explore innovative immunotherapies, maximize the tumor-killing efficacy of γδ T cells, and attenuate or eliminate tumor immunosuppression. (explorationpub.com)
  • Several genes of the C-type lectin superfamily, including the rodent NKRP1 family of glycoproteins, are expressed by NK cells and may be involved in the regulation of NK cell function. (thermofisher.com)
  • It is closely associated with B cell-activating factor of the TNF family (BAFF) receptor, transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) [ 14 ]. (biomedcentral.com)
  • Death receptor 6 (DR6), also known as tumor necrosis factor receptor superfamily member 21 (TNFRSF21), is a cell surface receptor of the tumor necrosis factor receptor superfamily which activates the JNK and NF-κB pathways. (wikipedia.org)
  • In this context, a new molecule, B-cell activating factor (BAFF), has emerged as a positive regulator of B cell survival and differentiation functioning through various signaling pathways and potentiating the activity of various receptor complexes through pleiotropic means. (medsci.org)
  • Phosphorylation of various TRAF proteins results in activation of both canonical and non-canonical NF-kB pathways. (biomedcentral.com)
  • TNF (Tumor necrosis factor) is a pleiotropic cytokine that plays an important role in immunity and inflammatory bone destruction. (frontiersin.org)
  • OBJECTIVE- Chronic activation of the nuclear factor-κB (NF-κB) in white adipose tissue leads to increased production of pro-inflammatory cytokines, which are involved in the development of insulin resistance. (diabetesjournals.org)
  • Using mice lacking the DNA hydroxymethylase TET2, we showed the requirement for TET2 in optimal production of hallmark cytokines by ILC3s and interleukin-17A (IL-17A) by inflammatory ILC2s. (stanford.edu)
  • Under inflammatory conditions, abnormal osteoclast differentiation and function often results in excessive bone resorption, which is a common characteristic of many diseases, such as osteoporosis, rheumatoid arthritis (RA), psoriatic arthritis and periodontitis ( 1 - 5 ). (frontiersin.org)
  • PTX3 expression was also up-regulated in a bone metastatic breast cancer cell line and further enhanced by pro-inflammatory cytokine TNFα. (oncotarget.com)
  • Cytokines are important in asthma and play a critical role in orchestrating the allergic inflammatory response, although the precise role of each cytokine remains to be determined. (cdc.gov)
  • [15] The production of NF-kB1 and ReIA increases rates of gene transcription of cytokines and inflammatory-inducing molecules. (wikidoc.org)
  • We previously showed that tumor-free peritoneum of patients with epithelial ovarian cancer (EOC) exhibited enhanced expression of several inflammatory response genes compared to peritoneum of benign disease. (biomedcentral.com)
  • The involvement of CD40 in chronic immune activation has resulted in CD40 being proposed as a therapeutic target for a range of chronic inflammatory diseases. (biomedcentral.com)
  • Disruption of this signaling pathway has the potential to reduce production of proinflammatory cytokines, reduce T helper cell function, and inhibit macrophage activation, making it a very attractive therapeutic target for patients with chronic inflammatory disease [ 3 ]. (biomedcentral.com)
  • Several days to weeks into the disease, development of immune anergy - or compensatory anti-inflammatory response syndrome - has been described in patients (74), associated with infection of pancreatic necrosis and multi-system organ failure. (pancreapedia.org)
  • The protein encoded by this gene is a member of the TNF-receptor superfamily. (wikipedia.org)
  • B-cell activating factor ( BAFF ) also known as tumor necrosis factor ligand superfamily member 13B is a protein that in humans is encoded by the TNFSF13B gene . (wikidoc.org)
  • Gene landscape and correlation between B-cell infiltration and programmed death ligand 1 expression in lung adenocarcinoma patients from The Cancer Genome Atlas data set. (cancer-genetics.org)
  • Lymphotoxin-alpha (LT-α) or tumor necrosis factor-beta (TNF-β) is a protein that in humans is encoded by the LTA gene . (wikidoc.org)
  • In other studies, mice with gene knockout of LT-α showed enhanced tumor growth, implicating possible protective role of LT-α in cancer. (wikidoc.org)
  • NKR-P1A, the receptor encoded by the KLRB1 gene, recognizes Lectin Like Transcript-1 (LLT1) as a functional ligand. (thermofisher.com)
  • citation needed] APP (amyloid precursor protein) is the natural ligand of DR6 and is first cleaved into Aβ and N-APP. (wikipedia.org)
  • These observations stimulated an intensive search for the mechanisms regulating tumor angiogenesis. (hindawi.com)
  • These results suggest genotoxic damage may induce a unique cancer-prone phenotype and processes mimicking activated B cell response to antigenic agents, as well as the normal B cell maturation processes. (biomedcentral.com)
  • Pathophysiologically, asthma exert different effects at different concentrations, can is characterized by constriction of airway smooth synergize or antagonize the effects of other cytokines muscle, hyper secretion of mucus, edema and airway and regulated in a complex manner and function via hyper responsiveness (AHR),[3] mucus secretion and cytokine cascade. (cdc.gov)
  • BAFF is a cytokine that belongs to the tumor necrosis factor (TNF) ligand family. (wikidoc.org)
  • NK cell infiltration into tumor tissue is associated with better disease prognosis in colorectal cancer, clear cell renal cell carcinoma, and lung carcinomas ( 9 - 11 ). (frontiersin.org)
  • During osteoclast differentiation, in a TMEM64 and ATP2A2-dependent manner induces activation of CREB1 and mitochondrial ROS generation necessary for proper osteoclast generation. (cusabio.com)
  • Results DIM, but not I3C, increased adipocyte differentiation through upregulation of peroxisome proliferator‐activated receptor γ and CCAAT/enhancer‐binding protein α. (researchgate.net)
  • Leptin and adiponectin can augment the oxidation of fatty acid in liver by activating the nuclear receptor super-family of transcription factors, namely peroxisome proliferator-activated receptor (PPAR)-α. (wjgnet.com)
  • These molecular mechanisms regulate osteoclast activation in different ways, but they are not isolated from each other. (bvsalud.org)
  • Recent studies have uncovered key intrinsic mechanisms by which TNF acts on osteoclast precursors to restrain osteoclastogenesis, including the mechanisms mediated by RBP-J signaling, RBP-J and ITAM (Immunoreceptor tyrosine-based activation motif) crosstalk, RBP-J mediated regulatory network, NF- κ B p100, IRF8, and Def6. (frontiersin.org)
  • TRAF6-dependent PI3K activation is a critical survival signal while TRAF2/TRAF6 have redundant functions in NF-kB activation and upregulation of CD80 and ICAM-1 expression [ 2 ]. (biomedcentral.com)
  • Canonical Notch signaling activates the transcription of BMI1 proto‑oncogene polycomb ring finger, cyclin D1, CD44, cyclin dependent kinase inhibitor 1A, hes family bHLH transcription factor 1, hes related family bHLH transcription factor with YRPW motif 1, MYC, NOTCH3, RE1 silencing transcription factor and transcription factor 7 in a cellular context‑dependent manner, while non‑canonical Notch signaling activates NF‑κB and Rac family small GTPase 1. (spandidos-publications.com)
  • [1] [2] Belonging to the hematopoietic cell line, LT-α exhibits anti-proliferative activity and causes the cellular destruction of tumor cell lines. (wikidoc.org)
  • [7] In contrast, unregulated expression of LT-α can result in a constantly active signaling pathway, thus leading to uncontrolled cellular growth and creation of tumors . (wikidoc.org)
  • We also highlight the therapeutic approaches aiming at targeting these regulators to enhance anti-tumor immunity. (mdpi.com)
  • Beyond GWAS—Could Genetic Differentiation within the Allograft Rejection Pathway Shape Natural Immunity to COVID-19? (mdpi.com)
  • The aim of this review is to describe the data linking PPARα and PPARγ to NAFLD/NASH and to discuss the use of PPAR ligands for the treatment of NASH. (wjgnet.com)
  • Cytokine that binds to TNFRSF11B/OPG and to TNFRSF11A/RANK. (cusabio.com)
  • Macrophages play a significant role in many processes, such as the human immune function, parasite infection, and tissue remodeling by secreting cytokines and producing reactive oxygen and nitrogen intermediates. (frontiersin.org)
  • Researchers have developed multiple intervention approaches to regulate macrophage/osteoclast activation. (bvsalud.org)
  • The CD56 bright population produces immunoregulatory cytokines, including interferon-γ (IFN-γ), tumor necrosis factor-beta (TNF-B), tumor necrosis factor-α (TNF-α), granulocyte macrophage-colony stimulating factor (GMCSF), IL-10, and IL-13 ( 4 ). (frontiersin.org)
  • A potential disadvantage of BCMA is that soluble BCMA can be released or shed from tumors into the the surrounding tissues and into the circulation. (biomedcentral.com)
  • Moreover, deletion of PDK1 in osteoclasts ameliorated osteolysis and rPDK1educed bone resorption markers in the murine model of prostate cancer-induced osteolysis. (bvsalud.org)
  • Although its actual cause remains still unknown, various environmental factors such as vitamin D deficiency, smoking, Epstein-Barr virus infection, and genetic factors have been accused as risk factors of the disease [ 1 ]. (medsci.org)
  • While it is known that genotoxic agents, such as IR, activate transcriptional programs involved in maintaining the integrity of the genome, we also want to investigate whether or not the genotoxic breaks could affect lymphocyte-specific maturation transcriptional responses similar to those we observed following RAG-induced physiological DSBs. (biomedcentral.com)
  • In addition, other bone and joint diseases related to osteoclast activation are also briefly introduced. (bvsalud.org)
  • The antitumor effect provided by natural killing has been observed in tumors of hematopoietic and non-hematopoietic origins and reported in diverse in vivo models and clinical series ( 8 ). (frontiersin.org)
  • Phase III clinical trials of Rova‑T for patients with small‑cell lung cancer and a phase III clinical trial of nirogacestat for patients with desmoid tumors are ongoing. (spandidos-publications.com)
  • Finally, it retrospectively analyze the activation strategies and clinical relevance of existing γδ T cell adoptive immunotherapies. (explorationpub.com)
  • The clinical significance of these events is highlighted by the utility of cytokine measurements in predicting outcome in human acute pancreatitis (116). (pancreapedia.org)
  • The potential therapeutic applications emerging from the roles of these cytokines will be discussed as well. (cdc.gov)
  • And it also has really key growth factors. (chiroeco.com)
  • So TGF-β, which is the transforming growth factor, IGF, which is insulin growth factor, which we know is related to growth hormone. (chiroeco.com)
  • And then we have what's called the VEGF, which is the vascular endothelial growth factor, which is responsible for formation of blood vessels, and then bFGF. (chiroeco.com)
  • [6] LT-α plays an important role in innate immune regulation and its presence has been shown to prevent tumor growth and destroy cancerous cell lines. (wikidoc.org)
  • CONCLUSION: These findings demonstrated that PDK1 performs an important role in osteoclastogenesis and prostate cancer-induced osteolysis by modulating the PDK1/AKT/NF-κB signaling pathway. (bvsalud.org)
  • Conclusions Our findings suggest that DIM may improve insulin sensitivity through the activation of the insulin signaling pathway, leading to enhanced glucose uptake. (researchgate.net)
  • Cytokines, cancer vaccines, adoptive cell transfers, and especially checkpoint inhibitors constitute valuable elements in the immunotherapeutic armamentarium. (frontiersin.org)
  • Since TAMs have been detected both in melanoma and non-melanoma skin cancer ( 8 , 12 - 14 ), their variable immunosuppressive function is determined by the stimulation from each cancer type and the corresponding stromal factors ( 11 , 13 , 15 , 16 ). (iiarjournals.org)