The molecular mechanism of Ang II induced-AAA models based on proteomics analysis in ApoE-/- and CD57BL/6J mice.

Apolipoprotein knockout (ApoE-/-) and CD57BL/6J mouse models of angiotensin II (Ang II)-induced abdominal aortic aneurysm (AAA) are commonly used in AAA research. However, the similarities and differences in the molecular mechanisms of AAA in these two genotypes have not been reported. In our study, we analyzed proteomics data from ApoE-/- and CD57BL/6J mouse models of Ang II-induced AAA and control mice by LC-MS/MS. Gene set enrichment analysis (GSEA) of differentially abundance proteins (DAPs) in the ApoE-/- or CD57BL/6J mouse groups was performed in R software, and infiltration of immune cells in groups was assessed. DAP that showed the same trend in abundance in ApoE-/- and CD57BL/6J mice (S-DAP) were identified and subjected to GO enrichment, KEGG pathway, and connectivity map (CMap) analyses. The protein-protein interaction (PPI) network of the S-DAP was drawn, the key S-DAP were identified by MCODE, and the transcription factors (TFs) of crucial S-DAP were predicted by iRegulon in Cytoscape. Male ApoE-/- and CD57BL/6J mouse models of Ang II-induced AAA are commonly used in AAA research, and extracellular matrix organization is associated with AAA in both of these models. However, there are some differences between the mechanisms underlying AAA in these two genotypes, and these differences need to be considered when studying AAA and selecting models. SIGNIFICANCE: Our research provided the first insight into the similarity and differential mechanisms of Ang II infused AAA models using ApoE-/- and CD57BL/6J mice. This study might provide the some advises for the selection of Ang II infused AAA models for further AAA researches.

Pro-and Anti-inflammatory Biomarkers as Potential Prognosis Markers in Oral Squamous Cell Carcinoma

ABSTRACT: The most widely used method to classify prognostic factors in cancers today is TNM. However, Oral Squamous Cell Carcinoma (OSCC) often demonstrates different behaviors in relation to aggressiveness and therapeutic response at the same TNM stage. So, in such cases biomarkers can be used to identify the biological diversity of these tumors more reliably, leading to better therapeutic strategies and disease management. The presence of inflammatory immune cells in the tumor microenvironment can have pro or antitumor effects and the investigation of the expression of inflammatory markers in OSSC can be usefulto design immunotherapeutic interventions. The Transforming Growth Factor alpha is a potent stimulator of cell migration that acts on cell proliferation, invasion and metastasis of cancer, as well as immune suppression and angiogenesis. Inflammatory cytokines, such as Interferon-gamma, mediate macrophage differentiation. Macrophages are an important component of the OSCC microenvironment. The greater amount of tumor-associated macrophages, especially the M2 phenotype, may be associated with a more aggressive biological behavior of the OSCC and, consequently, with reduced survival.

RESUMEN: El método más utilizado para clasificar los factores de pronóstico en los cánceres en la actualidad es TNM. Sin embargo, el carcinoma oral de células escamosas (COCE) a menudo muestra diferentes comportamientos en relación con la agresividad y la respuesta terapéutica en la misma etapa TNM. Entonces, en tales casos, los biomarcadores pueden usarse para identificar la diversidad biológica de estos tumores de manera más confiable, lo que lleva a mejores estrategias terapéuticas y manejo de la enfermedad. La presencia de células inmunes inflamatorias en el microambiente tumoral puede tener efectos pro o antitumorales y la investigación de la expresión de marcadores inflamatorios en COCE puede ser útil para diseñar intervenciones inmunoterapéuticas. El factor de crecimiento transformante α es un potente estimulador de la migración celular que actúa sobre la proliferación celular, la invasión y metástasis del cáncer, así como la inmunosupresión y la angiogénesis. Las citocinas inflamatorias, como el IFN-γ, median en la diferenciación de macrófagos. Los macrófagos son un componente importante del microambiente COCE. La mayor cantidad de macrófagos asociados a tumores, especialmente el fenotipo M2, puede estar asociada a un comportamiento biológico más agresivo del COCE y, en consecuencia, a una menor supervivencia.

Expression of epithelial growth factors and of apoptosis-regulating proteins, and presence of CD57+ cells in the development of inflammatory periapical lesions

Abstract The mechanisms that stimulate the proliferation of epithelial cells in inflammatory periapical lesions are not completely understood and the literature suggests that changes in the balance between apoptosis and immunity regulation appear to influence this process. Objective: To evaluate the expression of the epidermal growth factor (EGF), its receptor (EGFR) and of the keratinocyte growth factor (KGF), the presence of CD57+ cells, the epithelial cell proliferation index, and the expression of the Bcl-2 protein in inflammatory periapical lesions (IPL) at different stages of development. Methodology: Our sample was composed of 52 IPLs (22 periapical granulomas - PG - and 30 periapical cysts - PC), divided into three groups: PGs, small PCs, and large PCs. Specimens were processed for histopathologic and immunohistochemical analyses. Sections were evaluated according to the amount of positive staining for each antibody. Results: We found no significant differences among the groups regarding Bcl-2 (p=0.328) and Ki-67 (p>0.05) expression or the presence of CD57+ cells (p=0.748). EGF (p=0.0001) and KGF (p=0.0001) expression was more frequent in PCs than in PGs, and CD57+ cells were more frequent in IPLs with intense inflammatory infiltrates (p=0.0001). We found no significant differences in KGF (p=0.423), Bcl-2 (p=0.943), and EGF (p=0.53) expression in relation to inflammatory infiltrates or to the type of PC epithelial lining, but observed greater KGF expression (p=0.0001) in initial PCs. EGFR expression was similar among the groups (p>0.05). Conclusion: More frequent EGF and KGF expression in PCs and the greater presence of CD57+ cells in lesions with intense inflammatory infiltrates suggest that these factors influence IPL development. The greater KGF expression in initial PCs suggests its importance for the initial stages of PC formation.

Polyfunctional KLRG-1+CD57+ Senescent CD4+ T Cells Infiltrate Tumors and Are Expanded in Peripheral Blood From Breast Cancer Patients.

Senescent T cells have been described during aging, chronic infections, and cancer; however, a comprehensive study of the phenotype, function, and transcriptional program of this T cell population in breast cancer (BC) patients is missing. Compared to healthy donors (HDs), BC patients exhibit an accumulation of KLRG-1+CD57+ CD4+ and CD8+ T cells in peripheral blood. These T cells infiltrate tumors and tumor-draining lymph nodes. KLRG-1+CD57+ CD4+ and CD8+ T cells from BC patients and HDs exhibit features of senescence, and despite their inhibitory receptor expression, they produce more effector cytokines and exhibit higher expression of Perforin, Granzyme B, and CD107a than non-senescent subsets. When compared to blood counterparts, tumor-infiltrating senescent CD4+ T cells show similar surface phenotype but reduced cytokine production. Transcriptional profiling of senescent CD4+ T cells from the peripheral blood of BC patients reveals enrichment in genes associated with NK or CD8+-mediated cytotoxicity, TCR-mediated stimulation, and cell exhaustion compared to non-senescent T cells. Comparison of the transcriptional profile of senescent CD4+ T cells from peripheral blood of BC patients with those of HDs highlighted marked similarities but also relevant differences. Senescent CD4+ T cells from BC patients show enrichment in T-cell signaling, processes involved in DNA replication, p53 pathways, oncogene-induced senescence, among others compared to their counterparts in HDs. High gene expression of CD4, KLRG-1, and B3GAT1 (CD57), which correlates with increased overall survival for BC patients, underscores the usefulness of the evaluation of the frequency of senescent CD4+ T cells as a biomarker in the follow-up of patients.

NK Cell Activity and CD57+/NKG2Chigh Phenotype Are Increased in Men Who Have Sex With Men at High Risk for HIV.

Introduction: The HIV-exposed seronegative (HESN) status is for individuals who remain seronegative despite repeated exposure to HIV. One of the main cohorts within this group is men who have sex with men (MSM). Studies of this cohort have revealed different immunological and genetic mechanisms that can explain the phenomenon of natural HIV resistance. NK cells' higher effector capacity is related to natural resistance to HIV. Besides, a new population of NK cells with adaptive features was described recently. These cells are increased in some HESN cohorts and appear to be involved in better control of viral replication in primarily HIV-infected subjects. The present study evaluated the role of NK cells in the natural resistance to HIV-1 infection in MSM. Methodology: Phenotypic and functional features were evaluated in NK cells from two groups of MSM, at different risks of HIV infection, according to the number of sexual partners. The production of IFN-γ and ß-chemokines was included in the analysis, as well as the cytotoxic capacity and adaptive NK cell frequency. Genetic features, such as HLA and KIR allele frequencies, were also explored. Results: High-risk MSM exhibit an increased frequency of fully mature and CD57+/NKG2Chigh NK cells. These individuals also show higher cytotoxic capacity and IFN-γ production in response to K562 stimuli. NK cells with a CD107a+/IFN-γ+ functional profile were found more frequently and displayed higher IFN-γ production capacity among high-risk MSM than among low-risk MSM. The protective allele HLA-B∗18 was only present in the high-risk MSM group as well as HLA-B∗ 39. The protective phenotype KIR3DL1/S1-HLA-B∗Bw4, in a homozygous state, was particularly abundant in the high-risk population. Notably, some of these functional features were related to higher frequencies of mature and CD57+/NKG2Chigh NK cells, which, in turn, were associated with a higher number of sexual partners. Conclusion: The changes observed in the NK cell compartment can be driven by the magnitude of sexual exposure and immunological challenges of high-risk individuals, which could influence their resistance/susceptibility to HIV infection.

CD57 as a routine neuroendocrine marker for liver metastasis.

BACKGROUND: The characterization of hepatic metastases as having neuroendocrine origins is essential and the main markers currently used are chromogranin A (CgA) and synaptophysin (Syn). However, these markers may exhibit certain limitations, and the use of CD56 and CD57 can also be considered, although, due to low specificity, their use is discouraged. AIM: This study sought to compare the immunohistochemical expression of these markers in hepatic metastases of neuroendocrine neoplasms (NEN). MATERIALS AND METHODS: Eighteen samples, were used for immunohistochemical staining with CgA, Syn, CD56, and CD57 antibodies. The immunostaining reactions were compared according to its intensity (I), the percentage of labeled cells (P), and a final score (I × P). Statistical agreement between the markers was also evaluated. RESULTS: CD57 was expressed in the highest number of cases and also showed the most intense expression. CgA showed the highest number of cases with more than 80% positively stained area (72.2%), followed by CD57 (61.1%). The highest average score (I × P) was obtained for CD57 (9.1 ± 4.1). The best indices of agreement were between CgA and CD57 with respect to positivity (P = 0.021) and score (P = 0.014). According to the primary site, stomach/duodenum, lungs, and undetermined subgroups showed the highest average scores for CD57, followed by CgA. For the small bowel subgroup, the highest average score was obtained for CgA, followed by CD57. CONCLUSION: Our results highlight the importance of CD57 in the evaluation of hepatic metastases of NEN and indicate that this marker should be included with CgA and Syn in routine diagnostic panels.

Analysis of CD15, CD57 and HIF-1α in biopsies of patients with peri-implantitis.

Peri-implantitis is an infectious disease characterized by inflammation of the tissues surrounding the implant, bleeding on probing with or without suppuration, and bone loss. Peri-implant lesions contain a leukocyte infiltrate of plasma cells, lymphocytes, macrophages and neutrophils. A survey of the literature did not show any studies reporting an association between hypoxia and peri-implantitis. The aim of the present cross-sectional study was to evaluate histological changes and immunostaining for CD15, CD57 and HIF-1α in the peri-implant mucosa of patients with and without peri-implantitis. Mucosal biopsies were obtained from 18 patients with peri-implantitis and 10 control subjects without peri-implantitis at a private health care center between 2010 and 2012. The sections were fixed in 10% buffered formalin, processed and embedded in paraffin for histopathological and immunohistochemical study. Acanthosis, spongiosis and exocytosis were observed in both groups, with no significant difference between them. The peri-implantitis group showed increased immunostaining for CD15, a neutrophil marker, and HIF-1α, a tissue hypoxia marker, but no significant difference in immunostaining for CD57, a Natural Killer cell marker. The increase in neutrophil (CD15) and hypoxia (HIF-1α) markers in patients with peri-implantitis suggests an active participation of neutrophils and hypoxia in the pathogenesis of this disease. Since the present study was the first to evaluate the expression of CD15, CD57 and HIF-1α in peri-implant tissues, further studies should be performed to better understand the role of these molecules in peri-implantitis.

Prognostico valeu of intratumoral D57+T cells and microvessel density in head and neck squamous cell carcinoma / Valor prognóstico das células CD57+T e densidade dos microvasos no carcinoma de células escamosas de cabeça e pescoço

OBJECTIVES: This study aimed to examine the association of CD57+ T cells and MVD withclinical parameters and prognosis of HNSCC. MATERIAL AND METHOD: In a restrospectiveanalysis, 43 cases of primary HNSCC have been studied. We also analysed CD57 and CD31counting. T and N parameters was analized by Binary logistic regression analysis. Survival wasanalysed by Cox regression analysis. RESULTS: CD31 was not associated with anyclinicopathological parameters. CD57 immunoexpression was associated with locorregionalpresence. Cox regression test showed correlation of worse survival with locorregional metastasispresence. For binary logistic parameter, WHO Grade parameter was associated with smaller tumorsize and absent metastasis CD57+ T cells count was relationed with worse survival.CONCLUSION: There was no association between MVD and clinicopathological parameters.Locorregional metastasis presenting high CD57 positivity. No association was found betweenCD57 and the other clinicopathological parameters. Multivariate analysis showed that individualspresenting locorregional metastasis were associated with poor survival. CD57 count and WHOgrade were associated with larger tumor size.

OBJETIVO: Estudou-se a associação de células CD57+T e densidade microvascular comparâmetros clínicos e prognóstico do carcinoma de células escamosas de cabeça e pescoço(CCECP). MATERIAL E MÉTODO: Em análise retrospectiva, 43 casos de CCEP foramestudados. Analisamos também a contagem de CD57 e CD32. Os parâmetros T e N foramanalisados pela análise da regressão logística binária. A sobrevivência foi submetida a anális deregressão de Cox. RESULTADOS: CD31 não foi associada com nenhum parâmetroclinicopatológico. A imunoexpressão do CD57 associou-se com presença locorregional. O testede regressão de Cox demonstrou correlação entre pior sobrevivência com presença locorregionalde metástase. Para o parâmetro de logística binária, o parâmetro da OMS foi associado comtumores menores e ausência de metástases. A contagem das células CD57+ foi relacionada coma pior sobrevivência. CONCLUSÃO: Não houve associação entre microdensidade vascular eparâmetros clínico-patológicos. Metástases locorregionais apresentaram alta positividade paraCD57. Não foi encontrada associação entre CD57 e outros parâmetros clínico-patológicos. Análisemultivariada demonstrou que indivíduos apresentando metástases locorregionais apresentarampobre sobrevida. Contagem de CD57 e grau da OMS foram associados com tumores maiores.

Impact of cytomegalovirus and grafts versus host disease on the dynamics of CD57+CD28-CD8+ T cells after bone marrow transplant

OBJECTIVES: The present study aimed to evaluate the dynamics of CD28 and CD57 expression in CD8+ T lymphocytes during cytomegalovirus viremia in bone marrow transplant recipients. METHODS: In a prospective study, blood samples were obtained once weekly once from 33 healthy volunteers and weekly from 33 patients. To evaluate the expression of CD57 and CD28 on CD8+ T lymphocytes, flow cytometry analysis was performed on blood samples for four months after bone marrow transplant, together with cytomegalovirus antigenemia assays. RESULTS: Compared to cytomegalovirus-seronegative healthy subjects, seropositive healthy subjects demonstrated a higher percentage of CD57+ and a lower percentage of CD28+ cells (p<0.05). A linear regression model demonstrated a continuous decrease in CD28+ expression and a continuous increase in CD57+ expression after bone marrow transplant. The occurrence of cytomegalovirus antigenemia was associated with a steep drop in the percentage of CD28+ cells (5.94 percent, p<0.01) and an increase in CD57+ lymphocytes (5.60 percent, p<0.01). This cytomegalovirus-dependent effect was for the most part concentrated in the allogeneic bone marrow transplant patients. The development of acute graft versus host disease, which occurred at an earlier time than antigenemia (day 26 vs. day 56 post- bone marrow transplant), also had an impact on the CD57+ subset, triggering an increase of 4.9 percent in CD57+ lymphocytes (p<0.05). CONCLUSION: We found continuous relative changes in the CD28+ and CD57+ subsets during the first 120 days post- bone marrow transplant, as part of immune system reconstitution and maturation. A clear correlation was observed between the expansion of the CD57+CD28-CD8+ T lymphocyte subpopulation and the occurrence of graft versus host disease and cytomegalovirus viremia.