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.

Lymphopenia-induced proliferation of CD4 T-cells is associated with CD4 T-lymphocyte exhaustion in treated HIV-infected patients

Background & objectives: Under the lymphopenic condition, T-cells divide to maintain their peripheral pool size. Profound chronic lymphopenia in some treated HIV-infected patients, characterized by poor T-cell recovery, might result in intensive homeostatic proliferation and can cause T-cell exhaustion and/or senescence. The present study was undertaken to evaluate the homeostatic proliferation of CD4+T-cells in treated HIV-infected individuals, and to determine the amount of phenotypically exhausted and senescent CD4 T-lymphocytes. Methods: Thirty seven treated HIV-infected patients with suppressed HIV viral load (<50 copies/ml) were studied. Patients were divided into two groups: immunological non-responders (INRs) with CD4+T-cells <350/?l (n=16) and immunological responders (IRs) with CD4+T-cells >350/?l (n=21). T-cell subsets [na飗e, central memory (CM), and effector memory (EM)] and proportions of cycling (Ki-67+), senescent (CD57+) and exhausted (PD-1+) T-lymphocytes were assessed using flow cytometry. Results: CD4+T-cell cycling rate was higher in INRs than in IRs due to more extensive proliferation of CM, 4.7 vs 2.7 per cent (P <0.01) and EM, 4.8 vs 3.2 per cent (P <0.05). The percentages of CD4+Ki-67+ CM and EM T-lymphocytes were inversely related to the CD4+T-cell counts in the appropriate subset, r=�584 (P <0.001) and r=�556, (P <0.001), respectively. Exhaustion [24.2 vs 16.7% (P <0.01)], but not senescence [7.1 vs 10.8% (P>0.05)] was more pronounced in the INR group than in the IR group. The frequency of CD4+Ki-67+ CM T-cells was related to the proportion of CD4+PD-1+ cells of the same subset, r=0.789 (P <0.001). The numbers of CD4+Ki-67+PD-1+ CM and EM T-cells were substantially higher in INRs than in IRs. Interpretation & conclusions: The present data indicated that intensive homeostatic proliferation contributed to the T-cell exhaustion in HIV-infection.

CD57 (Leu-7, HNK-1) immunoreactivity seen in thin arteries in the human fetal lung / 대한해부학회지

CD57 (synonyms: Leu-7, HNK-1) is a well-known marker of nerve elements including the conductive system of the heart, as well as natural killer cells. In lung specimens from 12 human fetuses at 10–34 weeks of gestation, we have found incidentally that segmental, subsegmental, and more peripheral arteries strongly expressed CD57. Capillaries near developing alveoli were often or sometimes positive. The CD57-positive tissue elements within intrapulmonary arteries seemed to be the endothelium, internal elastic lamina, and smooth muscle layer, which corresponded to tissue positive for a DAKO antibody reactive with smooth muscle actin we used. However, the lobar artery and pulmonary arterial trunk as well as bronchial arteries were negative. Likewise, arteries in and along any abdominal viscera, as well as the heart, thymus, and thyroid, did not express CD57. Thus, the lung-specific CD57 reactivity was not connected with either of an endodermal- or a branchial arch-origin. CD57 antigen is a sugar chain characterized by a sulfated glucuronic acid residue that is likely to exist in some glycosphingolipids. Therefore, a chemical affinity or an interaction might exist between CD57-positive arterioles and glycosphingolipids originating from alveoli, resulting in acceleration of capillary budding to make contact with the alveolar wall. CD57 might therefore be a functional marker of the developing air-blood interface that characterizes the fetal lung at the canalicular stage.

A Case of Dendritic Cell Neurofibroma with Pseudorosettes / 대한피부과학회지

No abstract available.

The dynamic expression of CD57 on T cell and clinical significance analysis in acute HIV infection / 中华微生物学和免疫学杂志

ObjectiveTo study the dynamic express of CD57 on T cell of PBMC and clinical significance in acute HIV infection.MethodsSeventeen patients with acute HIV infection were enrolled study randomly diagnosed from 2006.11 to 2009.12 and 15 healthy donors as control group.The PBMCs from 1th,3th and 6th during acute infection were collected.The proportion of CD3+CD57+T lymphocytes,CD3+ CD8+CD57 +T lymphocytes and CD3 + CD4 + CD57 + T lymphocytes were evaluated by flow cytometric analysis with three or double color staining.The relationship between the proportion of CD57+ T phenotypes and virus load and CD4+T cells count was analyzed.ResultsThe proportion of CD57+T lymphocytes in PMBC in 1th,3th and 6th during acute HIV acute was 15.24％ ±1.49％,13.51％ ±2.45％ and 14.65％ ±1.83％,respectively,and was higher than normal control group and the difference was significantly(P＜0.0001 ).The proportion of CD8+ CD57+T lymphocytes was 7.79％ ±2.10％ and 9.88％ ±2.36％ in 1th and 3th month during acute infection,respectively.The proportion of CD8+ CD57+T lymphocytes in 1th and 3th month during acute infection were positive relationship with virus load in corresponding time,and R2 was 0.3700 and 0.3768,and P value was 0.0096 and 0.0088,respectively.The proportion of CD8+CD57+T lymphocytes in the 1th and 3th month during acute infection was negative relationship with CD4+T lymphocytes count.The R2 was 0.3768 and 0.4235,and P value was 0.0215 and 0.0017,respectively.In 6 rapid progressors and 11 no rapid progressors on the 1th month after HIV infection,CD8+ CD57+T lymphocytes percentage was 11.20％±2.21％ and 6.16％ ±1.09％,respectively,and CD4+CD57+T lymphocytes percentage 2.79％ ±0.31％and 1.40％ ±0.30％,respectively.Both CD8+CD57+T and CD4+CD57+T in rapid progressors were higher than no rapid progressors,and P value was 0.0338 and 0.0106,respectively.ConclusionCD57+ T lymphocytes percentage in peripheral blood increase in acute HIV infection patients,in which the increasing CD8+CD57+T lymphocyte may mirror the dynamic of HIV replication and CD4+T cell count.The CD57 high express on T lymphocyte on the early HIV acute infection predicts rapid progression.

The expression of CXCR5 and CD57 in autoimmune thyroid diseases / 中国综合临床

Objective To investigate the potential role of T follicular helper cells (Tfh) in the pathogenesis of autoimmune thyroid diseases by comparing the expression of C-X-C chemokine teceptor type 5 (CXCR5) and CD57 in Hashimoto's thyroiditis (HT) and Graves' disease (GD) thyroid tissues.Methods The expression of CXCR5 and CD57 proteins was determined by immunohistochemical analysis in 15 HT thyroid samples,18 GD samples and 10 normal thyroid samples.Results Immunohistochemical staining showed that CXCR5 and CD57 were mainly positive in cytomembrane and cytoplasm of the infiltrated lymphocytes both in HT and GD tissues,with much higher levels than that of normal thyroid tissues ( P ＜ 0.05 ).Both CXCR5 and CD57 were not significantly different between the HT and GD tissues.Conclusion CXCR5 and CD57 expressions were increased with a similar expression pattern in both of the two main autoimmune thyroid diseases( AITD),indicating that Tfh may participate inthe development and progression of AITD.

Loss of CD127 & increased immunosenescence of T cell subsets in HIV infected individuals.

Background & objectives: HIV infection is characterized by a perturbation in T cell homeostasis, leading to alteration in T cell subsets. In addition to alteration in differentiation, HIV infection also leads to change in T cell survival and regenerative capacity, as suggested by differential expression of CD127 and CD57. We evaluated the expression patterns of CD127 and CD57 on CD4 and CD8 effector, memory and naïve T cell subsets in HIV-infected and uninfected individuals. Methods: We characterized T cell subsets based on expression of these markers, and compared their expression pattern in HIV infected subjects and uninfected controls. We further assessed therapy generated changes in these subsets and expression of CD127 and CD57 on them. Results: There was a generalized decrease in naïve CD4 and CD8 T cells in HIV infected subjects. These changes in T cell subset distribution were related to antigen load. CD127 expression was significantly reduced in T cells from HIV infected subject. In association to this, HIV infected subjects had higher percentage of T cell subsets expressing CD57. Increased CD57 and reduced CD127 expression correlated with plasma viraemia and CD8 T cell activation state. Incomplete restoration of T cell subset proportions was observed, despite suppression of viral replication and increase in CD4 T cell counts. Further, the improvement was more pronounced in CD127 expression. Interpretation & conclusions: HIV infected subjects have reduced T cell regenerative capacity along with increased senescence, highlighting decreased proliferation and effector activities.

Association of CD57+ Natural Killer Cells with Better Overall Survival in DLBCL Patients

BACKGROUND: Malignant tumor cells may evoke the innate and adaptive immune systems. Various immune cells are involved in this immune reaction, and tumor infiltrating lymphocytes, macrophages, natural killer (NK) cells are associated with patient prognosis for solid tumors. METHODS: Seventy-eight patients who were diagnosed with diffuse large B cell lymphoma (DLBCL) between 2001 and 2009 were selected. CD57+ NK cells, CD68+ tumor associated macrophages (TAMs), and CD4+ and CD8+ T cells were evaluated in tissue sections using immunohistochemical staining and compared with clinical parameters including age, gender, performance status, clinical stage, serum lactic dehydrogenase level, number of extranodal sites, international prognostic index score, chemotherapy response, and survival. RESULTS: Patients with high numbers of CD57+ NK cells had a significantly higher overall survival rate than patients with low numbers of CD57+ NK cells. However, no significant difference was observed between the number of CD57+ NK cells and other prognostic parameters. The number of CD68+ TAMs and CD4+ or CD8+ T cells was not significantly correlated with prognostic factors in patients with DLBCL. CONCLUSIONS: An evaluation of tumor infiltrating CD57+ NK cells is recommended as a prognostic indicator in patients with DLBCL.

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.

The immunohistochemical study of the macrophages and natural killer cells in hepatocellular carcinoma tissues / 医学研究生学报

Objective:To investigate the number and distribution of macrophages (Mφ) and natural killer(NK) cells in hepatocellular carcinoma (HCC), paraneoplastic,cirrhosis and normal liver tissues and their relationship with the prognosis of HCC patients.　Methods:Surgical specimens from 60 cases of HCC, 62 cases of cirrhosis and 23 cases of normal liver tissues were investigated by immunohistochemical staining of CD68 and CD57 with a streptavidin-horseradish peroxidase detective system.The correlation of the number of Mφ and NK cells in different tissues with the clinical tumor parameters was also studied.　Results:①The order of the number of Mφ from the highest to the lowest was:paraneoplastic,cirrhosis, normal, HCC(P<0.05)；and the number of NK cells from the highest to the lowest was:HCC, paraneoplastic, normal, cirrhosis(P<0.05).②The number of Mφ decreased successively with the decrease of the HCC differentiation(P<0.05)；There was no relationship between the number of NK cells in HCC and histological grade. ③There was no relationship between the number of Mφ in HCC and clinical TNM stage ；The number of NK cells in HCC had degressive tendency with the clinical TNM stage(P<0.05). ④The number of Mφ and NK cells in HCC in the cases with metastasis in 15 months was significantly lower than that without metastasis(P<0.05, 0.01）.⑤There was a linear positive correlation between the number of Mφ and NK cells in HCC (r＝0.344, P<0.05).　Conclusion:The number of Mφ and NK cells in HCC in the cases with metastasis is significantly lower than that without metastasis；The number of Mφ has a close correlation with the HCC differentiation, and positive correlation with the number of NK cells；The number of Mφ and NK cells might be important markers to estimate the immune status and useful factors to predict the prognosis of HCC patients.