scholarly journals CA-125 of fetal origin can act as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin

2014 ◽  
Vol 19 (2) ◽  
Author(s):  
Ninoslav Mitić ◽  
Bojana Milutinović ◽  
Miroslava Janković
Keyword(s):  
Dendritic Cell ◽  
Fluid Phase ◽  
Structural Heterogeneity ◽  
Ca 125 ◽  
Coelomic Epithelium ◽  
Adhesion Receptor ◽  
Fetal Origin ◽  
Binding Inhibition ◽  
Subset Diversity ◽  
Recognition Molecule

AbstractCA-125 (coelomic epithelium-related antigen) forms the extracellular portion of transmembrane mucin 16 (MUC16). It is shed after proteolytic degradation. Due to structural heterogeneity, CA-125 ligand capacity and biological roles are not yet understood. In this study, we assessed CA-125 as a ligand for dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN), which is a C-type lectin showing specificity for mannosylated and fucosylated structures. It plays a role as a pattern recognition molecule for viral and bacterial glycans or as an adhesion receptor. We probed a human DC-SIGN-Fc chimera with CA-125 of fetal or cancer origin using solid- or fluid-phase binding and inhibition assays. The results showed that DC-SIGN binds to CA-125 of fetal origin and that this interaction is carbohydrate-dependent. By contrast, cancerderived CA-125 displayed negligible binding. Inhibition assays indicated differences in the potency of CA-125 to interfere with DC-SIGN binding to pathogen-related glycoconjugates, such as mannan and Helicobacter pylori antigens. The differences in ligand properties between CA-125 of fetal and cancer origin may be due to specificities of glycosylation. This might influence various functions of dendritic cells based on their subset diversity and maturation-related functional capacity.

scholarly journals The Dendritic Cell-Specific Adhesion Receptor DC-SIGN Internalizes Antigen for Presentation to T Cells

2002 ◽  
Vol 168 (5) ◽  
pp. 2118-2126 ◽  
Author(s):  
Anneke Engering ◽  
Teunis B. H. Geijtenbeek ◽  
Sandra J. van Vliet ◽  
Mietske Wijers ◽  
Ellis van Liempt ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cell ◽  
Adhesion Receptor

scholarly journals A Personalized Neoantigen Vaccine in Combination with Platinum-Based Chemotherapy Induces a T-Cell Response Coinciding with a Complete Response in Endometrial Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5801
Author(s):  
Alexandre Harari ◽  
Apostolos Sarivalasis ◽  
Kaat de Jonge ◽  
Anne-Christine Thierry ◽  
Florian Huber ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Endometrial Adenocarcinoma ◽  
Dendritic Cell Vaccine ◽  
Standard Of Care ◽  
T Cell Response ◽  
Ca 125 ◽  
Cell Vaccine ◽  
Gynecological Malignancy ◽  
Metastatic Recurrence ◽  
Platinum Based Chemotherapy

Endometrial cancer (EC) is a common gynecological malignancy and the fourth most common malignancy in European and North American women. Amongst EC, the advanced serous, p53-mutated, and pMMR subtypes have the highest risk of relapse despite optimal standard of care therapy. At present, there is no standard of care maintenance treatment to prevent relapse among these high-risk patients. Vaccines are a form of immunotherapy that can potentially increase the immunogenicity of pMMR, serous, and p53-mutated tumors to render them responsive to check point inhibitor-based immunotherapy. We demonstrate, for the first time, the feasibility of generating a personalized dendritic cell vaccine pulsed with peptide neoantigens in a patient with pMMR, p53-mutated, and serous endometrial adenocarcinoma (SEC). The personalized vaccine was administered in combination with systemic chemotherapy to treat an inoperable metastatic recurrence. This treatment association demonstrated the safety and immunogenicity of the personalized dendritic cell vaccine. Interestingly, a complete oncological response was obtained with respect to both radiological assessment and the tumor marker CA-125.

scholarly journals An acidic microenvironment sets the humoral pattern recognition molecule PTX3 in a tissue repair mode

2015 ◽  
Vol 212 (6) ◽  
pp. 905-925 ◽  
Author(s):  
Andrea Doni ◽  
Tiziana Musso ◽  
Diego Morone ◽  
Antonio Bastone ◽  
Vanessa Zambelli ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Innate Immunity ◽  
Tissue Repair ◽  
Fluid Phase ◽  
Metabolic Adaptation ◽  
Fibrin Deposition ◽  
Intact Molecule ◽  
Pattern Recognition Molecule ◽  
Recognition Molecule

Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule and a key component of the humoral arm of innate immunity. In four different models of tissue damage in mice, PTX3 deficiency was associated with increased fibrin deposition and persistence, and thicker clots, followed by increased collagen deposition, when compared with controls. Ptx3-deficient macrophages showed defective pericellular fibrinolysis in vitro. PTX3-bound fibrinogen/fibrin and plasminogen at acidic pH and increased plasmin-mediated fibrinolysis. The second exon-encoded N-terminal domain of PTX3 recapitulated the activity of the intact molecule. Thus, a prototypic component of humoral innate immunity, PTX3, plays a nonredundant role in the orchestration of tissue repair and remodeling. Tissue acidification resulting from metabolic adaptation during tissue repair sets PTX3 in a tissue remodeling and repair mode, suggesting that matrix and microbial recognition are common, ancestral features of the humoral arm of innate immunity.

Monoclonal antibodies against neoantigens of the terminal C5b-9 complex of human complement

1985 ◽  
Vol 5 (8) ◽  
pp. 649-658 ◽  
Author(s):  
Ferdinand Hugo ◽  
Dieter Jenne ◽  
Sucharit Bhakdi
Keyword(s):  
Monoclonal Antibodies ◽  
Cell Membranes ◽  
Animal Species ◽  
Fluid Phase ◽  
Double Diffusion ◽  
Human Complement ◽  
Complement Components ◽  
Binding Inhibition ◽  
Terminal Complexes

Assembly of the terminal C5b-C9 complement components into the cytolytic C5b-9 complex is accompanied by exposure of characteristic neoantigens on the macromolecule. We report the production and characterization of mouse monoclonal antibodies to C9-dependent neoantigens of human C5b-9. Binding-inhibition assays with EDTA-human plasma and micro-ELISA assays with purified C9 showed that the antibodies did not react with native complement components and thus confirmed the specificity of the antibodies for the neoantigens. The monoclonal antibodies did, however, cross-react with cytolyticaIly inactive, fluid-phase C5b-9 complexes, Thus, expression of the neoantigenic determinants was not dependent on the formation of high molecular weight C9 polymers with the complex, since these are absent in fluid-phase C5b-9. Radioiodinated antibodies could be utilized in immunoradiometric assays for the detection and quantitation of C5b-9 on cell membranes. Cross-reactivities of the antibodies with C9-dependent neoantigens of several other animal species were examined and antibody clones cross-reacting with rabbit (clones 3BI, 3Dg, and 2F3), sheep (clones 3Dg and 2F3) and guinea-pig (clone 3D8) neoantigens were identified. Three of four tested clones (3D8, 2F3, IA12) precipitated C5b-9 complexes in double-diffusion assays, probably due to their interaction with multiple and repeating C9-epitopes on the terminal complexes. The monoclonal antibodies will be of value for definitive identification and quantitation of C5b-9 on cell membranes and in tissues, and for establishing immunoassays for detection and quantitation of terminal fluid-phase C5b-9 complexes in plasma.

scholarly journals PTX3, a Humoral Pattern Recognition Molecule, in Innate Immunity, Tissue Repair, and Cancer

2018 ◽  
Vol 98 (2) ◽  
pp. 623-639 ◽  
Author(s):  
Cecilia Garlanda ◽  
Barbara Bottazzi ◽  
Elena Magrini ◽  
Antonio Inforzato ◽  
Alberto Mantovani
Keyword(s):  
Pattern Recognition ◽  
Innate Immunity ◽  
Tissue Repair ◽  
Human Genetics ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Fluid Phase ◽  
Viral Origin ◽  
Pattern Recognition Molecule ◽  
Recognition Molecule

Innate immunity includes a cellular and a humoral arm. PTX3 is a fluid-phase pattern recognition molecule conserved in evolution which acts as a key component of humoral innate immunity in infections of fungal, bacterial, and viral origin. PTX3 binds conserved microbial structures and self-components under conditions of inflammation and activates effector functions (complement, phagocytosis). Moreover, it has a complex regulatory role in inflammation, such as ischemia/reperfusion injury and cancer-related inflammation, as well as in extracellular matrix organization and remodeling, with profound implications in physiology and pathology. Finally, PTX3 acts as an extrinsic oncosuppressor gene by taming tumor-promoting inflammation in murine and selected human tumors. Thus evidence suggests that PTX3 is a key homeostatic component at the crossroad of innate immunity, inflammation, tissue repair, and cancer. Dissecting the complexity of PTX3 pathophysiology and human genetics paves the way to diagnostic and therapeutic exploitation.

scholarly journals The Effect of Surgical Intervention of Endometriosis to CA-125 and Pain

2020 ◽  
Vol 27 (6) ◽  
pp. 7-14
Author(s):  
Abdul Kadir Abdul Karim ◽  
Nor Haslinda Abd Aziz ◽  
Reena Rahayu Md Zin ◽  
Norfilza Mohd Mokhtar ◽  
Mohamad Nasir Shafiee
Keyword(s):  
Complex Disease ◽  
Surgical Intervention ◽  
Uterine Cavity ◽  
Ca 125 ◽  
Premature Menopause ◽  
Extensive Form ◽  
Coelomic Epithelium ◽  
Multiple Modalities ◽  
Elevated Expression ◽  
Vas Scores

Endometriosis is an inflammatory condition characterised by the presence of endometrial growth beyond the uterine cavity. It is a debilitating disease requiring multiple modalities of treatment. In considering surgery as the option of treatment, the benefits should outweigh the risk. Besides direct surgical risk, intervention may lead to a reduction of ovarian reserve, in addition to premature menopause and low fecundity. To date, there is an inconclusive evidence to support any specific parameters in monitoring disease progression following surgical intervention. Serum cancer antigen (CA)-125 is expressed by coelomic epithelium and has been extensively studied as a biomarker for endometriosis. Elevated expression of CA-125 has been shown in endometrial tissues and the marker increased indirectly from peritoneal irritation that accompanies an extensive form of endometriosis. Additionally, the visual analogue scale (VAS) scores have been used as an objective measurement for measuring pain, especially in a complex disease such as endometriosis. This review aims to consolidate a series of clinical trials that utilised CA-125 level and VAS score as tools for monitoring patients undergoing surgery for endometriosis.

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