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Diagnostic Pathology Feb 2020CD68+ tumor-associated macrophages (TAM) play an important role in the progression of classical Hodgkin lymphoma (cHL). We assessed the role of CD20 and CD68 + TAM in...
BACKGROUND
CD68+ tumor-associated macrophages (TAM) play an important role in the progression of classical Hodgkin lymphoma (cHL). We assessed the role of CD20 and CD68 + TAM in a cohort of cHL patients from Egypt and correlated the number of CD68 + cells with patients' characteristics, response to treatment, overall and progression free survival rates (OS & PFS).
METHODS
CD20 expression and CD68 + TAM numbers were assessed in representative tumor tissues obtained from 81 cHL patients using flowcytometry (FCM), immunohistochemistry (IHC), and Rt-PCR techniques.
RESULTS
The expression levels of CD68 protein by IHC was high in 27 (33.3%), moderate in 15 (18.5%), low in 15 (18.5%), and negative in 24 (29.6%) patients (p = 0.13). CD68-mRNA expression was high in 43/81(53.1%), and low in 38(46.9%) patients (p = 0.6). The number of CD68 + TAM (by FCM) was low (< 20 cells) in 42/81 (51.9%), and high (≥20 cells) in 39/81 (48.1%) patients (p = 0.74). CD68 expression (by FCM, IHC& Rt-PCR) associated significantly with poor response to treatment, decreased CD20 expression, reduced OS and PFS rates (p < 0.001 for all). CD68 expression (by Rt-PCR only) associated significantly with advanced disease stage (p = 0.04). The age of the patients, high CD20 expression & high CD68+ macrophage number were independent prognostic factors for OS (p= 0.02, p = 0.008 & p = 0.009; respectively). However, the age of the patient, high CD20, and high CD68+ macrophage expression (by FCM&IHC) were independent prognostic factors for DFS (p. = 0.004, p. = 0.01, p. = 0.007 and p. = 0.01; respectively).
CONCLUSION
CD68 + TAM expression (by Rt-PCR, FCM and/or IHC) can identify patients with poor response to treatment and reduced survival rates (OS& PFS). Assessment of CD68 + positive macrophages by FCM is superior to other methods (Rt-PCR and IHC) as a prognostic factor for DFS and OS rates.
Topics: Adolescent; Adult; Antigens, CD; Antigens, CD20; Antigens, Differentiation, Myelomonocytic; Cohort Studies; Egypt; Female; Hodgkin Disease; Humans; Immunohistochemistry; Macrophages; Male; Middle Aged; Neoplasm Staging; Prognosis; Retrospective Studies; Survival Rate; Young Adult
PubMed: 32019558
DOI: 10.1186/s13000-019-0912-3 -
Cytometry 1990It is possible accurately to distinguish lymphocytes from other leukocyte populations in peripheral blood using the combination of fluorescence associated with CD45/CD14... (Review)
Review
It is possible accurately to distinguish lymphocytes from other leukocyte populations in peripheral blood using the combination of fluorescence associated with CD45/CD14 and forward and orthogonal light scatter. By identifying the cell population of interest based on immunofluorescence, a light scattering window can then be drawn to include all (greater than or equal to 98%) of the lymphocytes. In this manner, maximal recovery of the lymphocytes within a sample can be consistently obtained. The combination of light scattering and immunofluorescence can also be used to define the purity of the gate. The identification of nonlymphocytes within the light scattering gate can then be used to establish an accurate denominator for the percent lymphocytes stained. Once the optimal data acquisition gate has been established and characterized, it is possible to correct subsequent analyses with that particular sample since the reactivity of monoclonal antibodies on monocytes and granulocytes can be accounted for once the nonlymphocytes have been identified as being within the acquisition gate.
Topics: Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, Myelomonocytic; Flow Cytometry; Fluorescent Antibody Technique; Histocompatibility Antigens; Humans; Leukocyte Common Antigens; Leukocytes; Light; Lipopolysaccharide Receptors; Lymphocytes; Monocytes; Scattering, Radiation
PubMed: 1693112
DOI: 10.1002/cyto.990110402 -
Chang Gung Medical Journal 2008CD152 or cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential receptor involved in the negative regulation of T cell activation. Because of its profound inhibitory... (Review)
Review
CD152 or cytotoxic T lymphocyte antigen-4 (CTLA-4) is an essential receptor involved in the negative regulation of T cell activation. Because of its profound inhibitory role, CD152 has been considered a sound susceptible candidate in autoimmunity and a persuasive target for cancer immunotherapy for over a decade. However, the precise roles played by this molecule continue to emerge. In particular, recent evidence suggests that CD152 is also important in the homeostasis and function of a population of suppressive cells, termed regulatory T cells (Treg). In this review, we discuss the recent progress and main features of monoclonal antibodies (mAbs) targeting CD152 and examine how each mAb prepared to a distinct epitope may impact differently upon CD152 modulation depending on its demonstrated regulatory role acting as an agonist, antagonist, or inverse agonist.
Topics: Amino Acid Sequence; Antibodies, Monoclonal; Antigens, CD; Antigens, Differentiation; Autoimmune Diseases; B7-1 Antigen; CD28 Antigens; CTLA-4 Antigen; Cell Adhesion; Humans; Molecular Sequence Data; Neoplasms; Protein Conformation; Signal Transduction; T-Lymphocytes, Regulatory
PubMed: 18419049
DOI: No ID Found -
Frontiers in Immunology 2018Activation of the T cell receptor (TCR) on the T cell through ligation with antigen-MHC complex of an antigen-presenting cell (APC) is an essential process in the...
Activation of the T cell receptor (TCR) on the T cell through ligation with antigen-MHC complex of an antigen-presenting cell (APC) is an essential process in the activation of T cells and induction of the subsequent adaptive immune response. Upon activation, the TCR, together with its associated co-receptor CD3 complex, assembles in signaling microclusters that are transported to the center of the organizational structure at the T cell-APC interface termed the immunological synapse (IS). During IS formation, local cell surface receptors and associated intracellular molecules are reorganized, ultimately creating the typical bull's eye-shaped pattern of the IS. CD6 is a surface glycoprotein receptor, which has been previously shown to associate with CD3 and co-localize to the center of the IS in static conditions or stable T cell-APC contacts. In this study, we report the use of different experimental set-ups analyzed with microscopy techniques to study the dynamics and stability of CD6-TCR/CD3 interaction dynamics and stability during IS formation in more detail. We exploited antibody spots, created with microcontact printing, and antibody-coated beads, and could demonstrate that CD6 and the TCR/CD3 complex co-localize and are recruited into a stimulatory cluster on the cell surface of T cells. Furthermore, we demonstrate, for the first time, that CD6 forms microclusters co-localizing with TCR/CD3 microclusters during IS formation on supported lipid bilayers. These co-localizing CD6 and TCR/CD3 microclusters are both radially transported toward the center of the IS formed in T cells, in an actin polymerization-dependent manner. Overall, our findings further substantiate the role of CD6 during IS formation and provide novel insight into the dynamic properties of this CD6-TCR/CD3 complex interplay. From a methodological point of view, the biophysical approaches used to characterize these receptors are complementary and amenable for investigation of the dynamic interactions of other membrane receptors.
Topics: Actins; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Biophysical Phenomena; CD3 Complex; Cell Line, Tumor; Fluorescent Antibody Technique; Humans; Immunological Synapses; Protein Binding; Protein Multimerization; Protein Transport; Receptor-CD3 Complex, Antigen, T-Cell; T-Lymphocytes
PubMed: 30356797
DOI: 10.3389/fimmu.2018.02333 -
Blood Reviews Dec 1992Aminopeptidases are a group of enzymes found on the cell surface and in the cytoplasmic compartments of many peripheral blood cell types and their progenitors. Their... (Review)
Review
Aminopeptidases are a group of enzymes found on the cell surface and in the cytoplasmic compartments of many peripheral blood cell types and their progenitors. Their functional roles include the hydrolysis of several biologically active peptides and growth factors and some have proved to be of diagnostic and prognostic value in leukaemia. These enzymes may also be found in serum as a consequence of non-haematopoietic related diseases and so have been used as indicators of liver damage. Haematopoietic cells in the bone marrow go through a process of growth and differentiation before being released into the peripheral circulation where they fulfill many functional roles. The enzyme activities of some aminopeptidases have been shown to modulate the growth of these cells. In addition, the activities of these enzymes themselves can be regulated by haematopoietic growth factors. However, the mechanisms that regulate their expression and activity are not fully understood. In this report the current literature has been reviewed for evidence of expression, regulation and clinical significance.
Topics: Aminopeptidases; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; CD13 Antigens; Cell Differentiation; Enzyme Induction; Hematopoietic Stem Cells; Humans; Oncogenes; Phosphorylation; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-fes; Substrate Specificity
PubMed: 1362509
DOI: 10.1016/0268-960x(92)90020-q -
The Journal of Clinical Investigation Feb 2002
Review
Topics: Abatacept; Animals; Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, T-Lymphocyte; B-Lymphocytes; CD28 Antigens; CTLA-4 Antigen; Cyclic AMP; Humans; Immunoconjugates; Inducible T-Cell Co-Stimulator Protein; Ligands; Lymphocyte Activation; Lymphocytes; Mice; Oncogene Proteins; Phosphatidylinositol 3-Kinases; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-vav; Signal Transduction; T-Lymphocytes
PubMed: 11827987
DOI: 10.1172/JCI14941 -
Journal of the American Society of... Dec 2016Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated...
Patients with ESRD undergoing peritoneal dialysis develop progressive peritoneal fibrosis, which may lead to technique failure. Recent data point to Th17-mediated inflammation as a key contributor in peritoneal damage. The leukocyte antigen CD69 modulates the setting and progression of autoimmune and inflammatory diseases by controlling the balance between Th17 and regulatory T cells (Tregs). However, the relevance of CD69 in tissue fibrosis remains largely unknown. Thus, we explored the role of CD69 in fibroproliferative responses using a mouse model of peritoneal fibrosis induced by dialysis fluid exposure under either normal or uremic status. We found that cd69 mice compared with wild-type (WT) mice showed enhanced fibrosis, mesothelial to mesenchymal transition, IL-17 production, and Th17 cell infiltration in response to dialysis fluid treatment. Uremia contributed partially to peritoneal inflammatory and fibrotic responses. Additionally, antibody-mediated CD69 blockade in WT mice mimicked the fibrotic response of cd69 mice. Finally, IL-17 blockade in cd69 mice decreased peritoneal fibrosis to the WT levels, and mixed bone marrow from cd69 and Rag2c mice transplanted into WT mice reproduced the severity of the response to dialysis fluid observed in cd69 mice, showing that CD69 exerts its regulatory function within the lymphocyte compartment. Overall, our results indicate that CD69 controls tissue fibrosis by regulating Th17-mediated inflammation.
Topics: Animals; Antigens, CD; Antigens, Differentiation, T-Lymphocyte; Female; Lectins, C-Type; Mice; Peritoneal Fibrosis; Th17 Cells
PubMed: 27151919
DOI: 10.1681/ASN.2015080909 -
Current Biology : CB Mar 2000The identification and characterization of a newly extended family of molecules related to the T-cell costimulatory proteins CD28 and B7 suggests that a distinct form of... (Review)
Review
The identification and characterization of a newly extended family of molecules related to the T-cell costimulatory proteins CD28 and B7 suggests that a distinct form of costimulatory signals could be important for effector T-cell responses outside of lymphoid tissues.
Topics: Abatacept; Amino Acid Sequence; Animals; Antigens, CD; Antigens, Differentiation; Antigens, Differentiation, T-Lymphocyte; B7-1 Antigen; CD28 Antigens; CTLA-4 Antigen; Cell Division; Humans; Immunoconjugates; Immunoglobulin Fc Fragments; Inducible T-Cell Co-Stimulator Protein; Ligands; Molecular Sequence Data; T-Lymphocytes
PubMed: 10744968
DOI: 10.1016/s0960-9822(00)00400-0 -
FEBS Letters Apr 2018Long intergenic noncoding RNAs (lincRNAs) are not fully characterized in disease, although many are involved in controlling differentiation. We discovered and sequenced...
Long intergenic noncoding RNAs (lincRNAs) are not fully characterized in disease, although many are involved in controlling differentiation. We discovered and sequenced a novel 4.4 kb human lincRNA called linc-9432 in pterygium, an ocular disease characterized by a wedge lesion. This transcript inhibited differentiation-induced cell death, promoted expression of stem cell markers, and decreased expression of epithelial and mesenchymal differentiation markers. This lincRNA regulated 30 differentiation-related genes in transcriptome analysis and 17/30 gene products were known to be directly associated in a network. When the lincRNA was silenced with pooled siRNA, the levels of these transcripts decreased in accordance with their predicted binding affinity for the lincRNA. TBC1D8B had the strongest affinity, interacting in-vitro at positions 269-292 within TBC1D8B.
Topics: Antigens, Differentiation; Cell Differentiation; Cells, Cultured; Female; Fibroblasts; Gene Expression Profiling; Gene Expression Regulation; Humans; Male; Pterygium; RNA, Long Noncoding
PubMed: 29513395
DOI: 10.1002/1873-3468.13027 -
Clinical and Experimental Allergy :... Mar 2009Siglecs (sialic acid-binding, Ig-like lectins) are a family of single-pass transmembrane cell surface proteins found predominantly on leucocytes. Their unique structural... (Review)
Review
Siglecs (sialic acid-binding, Ig-like lectins) are a family of single-pass transmembrane cell surface proteins found predominantly on leucocytes. Their unique structural characteristics include an N-terminal carbohydrate-binding ('lectin') domain that binds sialic acid, followed by a variable number of Ig-like domains, hence these structures are a subset of the Ig gene superfamily. Another unique feature of Siglecs is that most, but not all, possess so-called immunoreceptor tyrosine-based inhibitory motifs in their cytoplasmic domains, suggesting that these molecules function in an inhibitory capacity. Siglec-8, the eighth member identified at the time, was discovered as part of an effort initiated almost a decade ago to identify novel human eosinophil and mast cell proteins. Since that time, its selective expression on human eosinophils and mast cells has been confirmed. On eosinophils, Siglec-8 engagement results in apoptosis, whereas on mast cells, inhibition of FcepsilonRI-dependent mediator release, without apoptosis, is seen. It has subsequently been determined that the closest functional paralog in the mouse is Siglec-F, selectively expressed by eosinophils but not expressed on mast cells. Despite only modest homology, both Siglec-8 and Siglec-F preferentially recognize a sulphated glycan ligand closely related to sialyl Lewis X, a common ligand for the selectin family of adhesion molecules. Murine experiments in normal, Siglec-F-deficient mice and hypereosinophilic mice have resulted in similar conclusions that Siglec-F, like Siglec-8, plays a distinctive and important role in regulating eosinophil accumulation and survival in vivo. Given the resurgent interest in eosinophil-directed therapies for a variety of disorders, plus its unique additional ability to also target the mast cell, therapies focusing on Siglec-8 could some day prove to be a useful adjunct to our current armamentarium for the treatment of asthma, allergies and related disorders where overproduction and overactivity of eosinophils and mast cells is occurring.
Topics: Animals; Antigens, CD; Antigens, Differentiation, B-Lymphocyte; Antigens, Differentiation, Myelomonocytic; Eosinophils; Gene Expression; Humans; Lectins; Ligands; Mast Cells; Mice; Sialic Acid Binding Immunoglobulin-like Lectins
PubMed: 19178537
DOI: 10.1111/j.1365-2222.2008.03173.x