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1.
Anticancer Res ; 39(9): 4643-4652, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519562

RESUMO

BACKGROUND/AIM: Adenoviral-mediated expression of CD40 ligand (CD40L) on dendritic cells (DCs) activates immune check point CD40/CD40L, enhancing the immunostimulation of DCs and effector cells against human renal carcinoma cells (RCC) and inducing tumor cell apoptosis in vitro. MATERIALS AND METHODS: DCs, isolated from buffy coats from healthy donors, were transduced with adenoviruses carrying human CD40L (Ad-hCD40L). Subsequently maturation marker and cytokine expression were analyzed by fluorescence-activated cell sorting and enzyme-linked immunosorbent assay. RESULTS: Adenoviral transduction induced high expression of soluble CD40L and membrane-bound CD40L, leading to a strong CD40-CD40L interaction in DCs. Interestingly, a T-helper cell type 1 shift of expressed cytokines/chemokines was observed due to the expression of membrane-bound CD40L rather than due to soIuble CD40L alone, which significantly reduced immunoactivation of DCs. However, supernatants of Ad-hCD40L-transduced DCs induced apoptosis of RCC cells. Co-culture of Ad-hCD40L DCs with cytokine-induced killer cells led to a significant stimulation of tumor-specific cytokine-induced killer cells, with increased proliferation and cytotoxicity. CONCLUSION: Use of Ad-hCD40L-transduced DCs is a promising approach to treating RCC.


Assuntos
Antígenos CD40/metabolismo , Ligante de CD40/metabolismo , Carcinoma de Células Renais/metabolismo , Células Dendríticas/metabolismo , Imunomodulação , Neoplasias Renais/metabolismo , Adenoviridae/genética , Biomarcadores , Ligante de CD40/genética , Carcinoma de Células Renais/imunologia , Linhagem Celular Tumoral , Citocinas/metabolismo , Citotoxicidade Imunológica , Células Dendríticas/imunologia , Vetores Genéticos/genética , Humanos , Imunofenotipagem , Neoplasias Renais/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Transdução Genética
2.
Anticancer Res ; 39(9): 4699-4709, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519569

RESUMO

BACKGROUND/AIM: Metformin, a drug for type 2 diabetes, also exerts anticancer effects. This study addressed the immunological effects of metformin on peritoneal dissemination. MATERIALS AND METHODS: We developed a mouse model of peritoneal dissemination via intraperitoneal injection of RLmale1, an X-ray-induced leukemia cell line, into BALB/c mice. Cell-surface markers, cytokine production, and myeloid-derived suppressor cells (MDSCs) were examined in cells from spleen and peritoneal lavage fluid. RESULTS: Metformin-treated mice exhibited suppressed intraperitoneal tumor growth and extended survival, and these effects were lost in mice with severe combined immunodeficiency. MDSCs induction was inhibited in metformin-treated mice. Although MDSC mobilization into the peritoneal cavity was correlated with suppression of interferon-γ production by tumor-infiltrating lymphocytes, the T-helper 1 ability of these lymphocytes was preserved in metformin-treated mice. CONCLUSION: Our findings demonstrate the action of metformin on both intraperitoneal tumors and immune-suppressive cells and might contribute to the development of immunotherapy against peritoneal dissemination.


Assuntos
Imunomodulação/efeitos dos fármacos , Metformina/farmacologia , Neoplasias Peritoneais/imunologia , Neoplasias Peritoneais/patologia , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/imunologia , Animais , Biomarcadores , Linhagem Celular Tumoral , Modelos Animais de Doenças , Humanos , Imunofenotipagem , Masculino , Camundongos , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/imunologia , Células Supressoras Mieloides/metabolismo , Metástase Neoplásica , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/mortalidade , Modelos de Riscos Proporcionais , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Anticancer Res ; 39(9): 4845-4851, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519587

RESUMO

BACKGROUND/AIM: Triple-negative breast cancer (TNBC) constitutes 15-20% of all breast carcinomas, affecting younger women more often and has a worse prognosis than other types of breast cancer, due to the combination of more aggressive clinical behavior and lack of molecular targets for therapy. This study assessed the effects of non-genotoxic concentrations of tributyltin isothiocyanate (TBT-ITC) and triphenyltin isothiocyanate (TPT-ITC) on MDA-MB-231 cells. MATERIALS AND METHODS: MTT assay, comet assay, kinetic imaging and flow cytometry were used for analysis of MDA-MB-231 cells. RESULTS: The results showed that 100 nM concentration of TBT-ITC and TPT-ITC, that did not affect viability or DNA integrity, slowed-down migration by CD44 down-regulation. Moreover, both compounds demonstrated immunomodulatory properties, attenuating PD-L1 expression in MDA-MB-231 cells. CONCLUSION: TPT-ITC was more effective in down-regulating CD44 expression and reducing migration than TBT-ITC, while TBT-ITC was more potent in lowering PD-L1 expression in comparison with TPT-ITC.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais , Movimento Celular/efeitos dos fármacos , Isotiocianatos/farmacologia , Neoplasias de Mama Triplo Negativas/metabolismo , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Feminino , Humanos , Imunofenotipagem , Isotiocianatos/química , Compostos Orgânicos de Estanho/química
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(8): 766-771, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31416500

RESUMO

OBJECTIVE: To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥100×109/L; n=263) and thrombocytopenia group (platelet count <100×109/L; n=629). The thrombocytopenia group was further divided into (50- <100)×109/L (n=243), (20- <50)×109/L (n=263), and <20×109/L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed. RESULTS: Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P<0.05), as well as a significantly higher 10-year EFS rate (P<0.05). There was no significant difference in 10-year OS between the two groups (P>0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P<0.05), and there was still no significant difference in 10-year OS between the two groups (P>0.05). The <20×109/L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- <100)×109/L subgroup, and the (20- <50)×109/L subgroup (P<0.05). After the children with MLL gene rearrangement were excluded, the <20×109/L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50-<100)×109/L subgroup, and the (20- <50)×109/L subgroup (P<0.05). CONCLUSIONS: ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of <20×109/L have the worst prognosis.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Intervalo Livre de Doença , Humanos , Imunofenotipagem , Prognóstico , Recidiva
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(4): 1259-1264, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31418390

RESUMO

OBJECTIVE: To explore the role of bone marrow microenvironment(niche) in the development of acute myeloid leukemia (AML) and the effect of AML patients-derived MSC on the proliferation, cell cycle and immuno-phenotypes of HL-60 cells. METHODS: The MSC derived from bone marrow of patients with newly diagnosed AML were isolated and co-cultured with HL-60 cells. The effect of MSC on proliferation of HL-60 cells was detected by using 3H-TdR incorporation method, the cell cycle and immunophenotypes of HL-60 cells were detected by flow cytometry. RESULTS: The results of 3H-TdR incorporation assay showed that both AML-MSCs and normal MSCs remarkably suppressed the HL-60 cell proliferation in a time- and dose-dependent manner. The results of cell cycle analysis demonstrated that AML MSCs and normal MSCs induced arrest of the HL-60 cells in G0/G1 phase. The results of immunophenotyping revealed that MSCs suppressed the expression of CD11a and CD154 on the surface of HL-60 cells. Moreover, AML MSCs exhibited increased inhibitory effects than that of normal MSCs. However, no remarkable effect of MSCs on CD54 expressions of HL-60 cells was observed in the current study. CONCLUSION: AML-MSCs possess effects on HL-60 cell proliferation, cell cycle and immunophenotypes similiar to normal MSCs, but exhibited increased suppressive capacity on the expression of CD11a and CD154.


Assuntos
Leucemia Mieloide Aguda , Células-Tronco Mesenquimais , Células da Medula Óssea , Ciclo Celular , Proliferação de Células , Células HL-60 , Humanos , Imunofenotipagem , Microambiente Tumoral
6.
Presse Med ; 48(7-8 Pt 1): 816-824, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31439443

RESUMO

Diagnosis of mature B cell malignancies is highly multidisciplinary. Biological tools provide diagnostic, prognostic and theranostic information. Biological hematology allows considering mature B cell diseases from two perspectives : cellular and molecular approaches. Cytomorphology and flow cytometry are tools from cell hematology. Conventional cytogenetics, FISH and molecular biology are tools from molecular hematology. NGS is a new technique that could dramatically change diagnostic and therapeutic management of B cell malignancies in the near future. Integration of clinical, pathological and biological data allows for personalized management of these diseases.


Assuntos
Técnicas de Laboratório Clínico/métodos , Leucemia de Células B/diagnóstico , Linfoma de Células B/diagnóstico , Integração de Sistemas , Hibridização Genômica Comparativa/métodos , Citodiagnóstico/métodos , Análise Citogenética/métodos , Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Imunofenotipagem/métodos , Hibridização in Situ Fluorescente/métodos , Leucemia de Células B/genética , Leucemia de Células B/patologia , Linfoma de Células B/genética , Linfoma de Células B/patologia , Técnicas de Diagnóstico Molecular/métodos , Imagem Multimodal/métodos , Imagem Multimodal/tendências
7.
Presse Med ; 48(7-8 Pt 1): 807-815, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447332

RESUMO

Chronic lymphocytic leukemia is the most frequent adult leukemia. Eighty per cent of the patients are asymptomatic at diagnosis and 30% of the patients will be never treated. The diagnosis is based on the blood smear examination and immunophenotyping by flow cytometry of blood lymphocytes. The first line option is immunochemotherapy in 90% of the patients without genetic abnormalities associated with chemo resistance. The use of new compounds targeting different pathways is more frequent especially in relapsing patients and could be an alternative to the chemotherapy in the future. Asymptomatic patients with a stable disease assessed by the specialist can be followed by the general practitioner with a blood count and clinical examination every six months or once a year.


Assuntos
Leucemia Linfocítica Crônica de Células B , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia , Leucemia Linfocítica Crônica de Células B/classificação , Leucemia Linfocítica Crônica de Células B/diagnóstico , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/tendências , Prognóstico , Inibidores de Proteínas Quinases/uso terapêutico , Terapias em Estudo/métodos , Terapias em Estudo/tendências
8.
Presse Med ; 48(7-8 Pt 1): 850-858, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31447334

RESUMO

Follicular lymphoma, the second most common lymphoma, is characterized by its slow growth and is often considered incurable in advanced stages. Progresses in biology have contributed to better understand the complex and successive mechanisms of development of this pathology, whose diagnosis is based on a lymph node biopsy. However, the prognosis of the patients is heterogeneous and several indexes have been proposed to identify groups of patients with a similar life expectancy, in order to guide the therapeutic choices. The treatment has been modified in the last 20 years by the emergence of anti-CD20 monoclonal antibodies which constitute, alone or in combination, of the cornerstone of therapeutic management. After staging using, in particular, 18-fluorodeoxyglucose positron emission tomography, the therapeutic strategy will be adapted for each patient, ranging from simple watchful waiting to a combination of chemotherapy and anti-CD20 antibodies. Relapses (which often require a new lymph node biopsy to eliminate a possible histological transformation into an aggressive lymphoma with poorer prognosis) remain common but are still accessible to effective therapeutic interventions. Thanks to these advances, the median life expectancy of patients with follicular lymphoma now exceeds 15 years.


Assuntos
Linfoma Folicular , Biópsia , Diagnóstico Diferencial , Humanos , Imunofenotipagem/métodos , Imunoterapia/métodos , Imunoterapia/tendências , Expectativa de Vida , Linfoma Folicular/diagnóstico , Linfoma Folicular/epidemiologia , Linfoma Folicular/patologia , Linfoma Folicular/terapia , Técnicas de Diagnóstico Molecular , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/terapia , Medicina de Precisão/métodos , Medicina de Precisão/tendências , Prognóstico , Taxa de Sobrevida , Terapias em Estudo/métodos , Terapias em Estudo/tendências
9.
Zhonghua Xue Ye Xue Za Zhi ; 40(6): 512-517, 2019 Jun 14.
Artigo em Chinês | MEDLINE | ID: mdl-31340626

RESUMO

Objective: To compare the sensitivity of 8-color panels and next generation flow cytometry (NGF) for detecting minimal residual disease of multiple myeloma patients. Methods: 8-color-membrane antigens (8C-Mem) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, CD27 and CD117 to identify the plasma cells, while 8-color-cytoplasmic antigens (8C-Cyto) panel was built including CD45, CD38, CD138, CD19, CD56, CD81, cKappa (cK) and cLambda (cλ) , and 8-color-two-tubes (8C-2tubes) panel were built including 8C-Mem and 8C-Cyto panels, the data of three groups was analyzed by Diva software. NGF uses Infinicyt software to fuse 8C-2tubes data to further analyze the expression of plasma antigens. Bone marrow aspiration obtained from 20 controls and 76 multiple myeloma patients who achieved complete remission were measured and analyzed. Results: Positive MRD samples were discriminated in 88.2% of the specimen evaluated through either abnormal plasma cells (aPCs) or clonal plasma cells (cPCs) by NGF antigens panel, Among of them, consistency was 94.7%. The median percentage of cPCs was 0.3530%, The lowest sensitivity of NGF was 0.0003%. In 8-color panels, the positive MRD rates of 8C-Mem, 8C-Cyto and 8C-2tubes panels were 84.2%, 85.5% and 86.8%, respectively, which lower than that of NGF (P<0.001) . The positive MRD rate of 8C-Mem and 8C-Cyto panels were lower than that of 8C-2tubes panel (P<0.001) , and the positive MRD rate of 8C-Mem panel was lower than that of 8C-Cyto panel (P<0.001) . Sensitivity and specificity of NGF was higher than that of 8-color panels. 8C-2tubes panel has the best sensitivity, accuracy, negative predicted value, positive predicted value and specificity than other 8-color panels. However, huge data and low efficiency for analysis is the disadvantage. 8C-Cyto panel was the second choice, and 8C-Mem panel was the last. Conclusions: Membrane and cytoplasmic light chain is a better method for multiple myeloma-MRD detection and NGF panel is an ideal approach. 8C-Cyto panel is recommended in 8-MFC groups.


Assuntos
Mieloma Múltiplo , Medula Óssea , Citometria de Fluxo , Humanos , Imunofenotipagem , Mieloma Múltiplo/diagnóstico , Neoplasia Residual , Plasmócitos
10.
Vet Immunol Immunopathol ; 213: 109889, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31307671

RESUMO

Blocking immunoglobulin G (IgG) binding receptors on leukocytes is an established and highly recommended preventive procedure for immunological assays. Failing to prevent such nonspecific binding can lead to erroneous results. Several studies testing different blocking reagents have been performed in murine or human cells, however, there are no specific studies on bovine cells. Our study aimed to investigate the efficiency of blocking reagents to inhibit the nonspecific binding of mouse monoclonal antibodies (mAbs) to bovine peripheral blood cells. We observed nonspecific interactions of IgG2a and IgG2b negative isotypes with bovine leukocytes, but not IgG1. We found that these nonspecific bindings could be eliminated by blocking with purified mouse IgG, whereas little or no blocking effect was observed when bovine serum or Mouse Seroblock FcR were applied. Moreover, in the absence of an efficient blocking reagent, the percentage of CD335 positive cells was significantly higher than in the group previously blocked with mouse IgG. Based on these results, and due to the lack of specific commercial blocking reagents for bovine cells, our recommendation is to use purified mouse IgG as a blocking reagent for immune assays targeting bovine leukocytes in order to enhance the accuracy of the results.


Assuntos
Anticorpos Monoclonais/imunologia , Imunofenotipagem/métodos , Leucócitos Mononucleares/imunologia , Receptores Fc/imunologia , Erro Experimental , Animais , Bovinos , Epitopos/imunologia , Citometria de Fluxo , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Imunofenotipagem/normas , Camundongos , Ligação Proteica
11.
Braz J Infect Dis ; 23(3): 151-159, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31271732

RESUMO

BACKGROUND: HIV infection harms adaptive cellular immunity mechanisms. Long-term virological control by combined antiretroviral therapy (cART) reduces the risk of mycobacterial infections. Thus, we aimed to study cellular responses to mycobacterial antigens in 20 HIV-infected adolescents with at least one year of virological control (HIV-RNA <40 copies/mL) and 20 healthy adolescents. METHODS: We evaluated CD8 and γδ T-cell degranulation by measurement of CD107a membrane expression after stimulation with lysates from BCG (10 µg/mL) and H37RA Mycobacterium tuberculosis (Mtb, 10 µg/mL). Immune activation and antigen-presenting ability were also assessed by determination of HLA-DR, CD80, and CD86 markers. RESULTS: TCR γδ T-cell CD107a expression was similar between groups in response to mycobacterial antigens, and lower in the HIV-infected group in response to mitogen. Higher baseline HLA-DR expression and lower mycobacterial-stimulated expression was found within the HIV-infected group. CONCLUSIONS: Similar degranulation in stimulated CD8+ and TCR γδ T-cells from HIV-infected adolescents, when compared to healthy controls suggests long-term immunological preservation with immune reconstitution under successful cART. However, differences in HLA-DR expression may represent ongoing inflammation and lower specific responses in HIV-infected youth. These features may be relevant in the context of the precocity and severity of vertically acquired HIV infection.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/imunologia , Fármacos Anti-HIV/uso terapêutico , Antígenos de Bactérias/imunologia , Linfócitos T CD8-Positivos/imunologia , Mycobacterium tuberculosis/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Tuberculose/imunologia , Apresentação do Antígeno/imunologia , Antígenos de Bactérias/efeitos dos fármacos , Biomarcadores/sangue , Estudos Transversais , Feminino , Humanos , Imunofenotipagem , Transmissão Vertical de Doença Infecciosa , Masculino , Estudos Prospectivos , Adulto Jovem
13.
BMC Bioinformatics ; 20(Suppl 5): 181, 2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31272372

RESUMO

BACKGROUND: Within the cancer domain, ontologies play an important role in the integration and annotation of data in order to support numerous biomedical tools and applications. This work seeks to leverage existing standards in immunophenotyping cell types found in hematologic malignancies to provide an ontological representation of them to aid in data annotation and analysis for patient data. RESULTS: We have developed the Cancer Cell Ontology according to OBO Foundry principles as an extension of the Cell Ontology. We define classes in Cancer Cell Ontology by using a genus-differentia approach using logical axioms capturing the expression of cellular surface markers in order to represent types of hematologic malignancies. By adopting conventions used in the Cell Ontology, we have created human and computer-readable definitions for 300 classes of blood cancers, based on the EGIL classification system for leukemias, and relying upon additional classification approaches for multiple myelomas and other hematologic malignancies. CONCLUSION: We have demonstrated a proof of concept for leveraging the built-in logical axioms of the ontology in order to classify patient surface marker data into appropriate diagnostic categories. We plan to integrate our ontology into existing tools for flow cytometry data analysis to facilitate the automated diagnosis of hematologic malignancies.


Assuntos
Ontologias Biológicas , Neoplasias Hematológicas/patologia , Linhagem Celular Tumoral , Neoplasias Hematológicas/classificação , Neoplasias Hematológicas/metabolismo , Humanos , Imunofenotipagem , Aprendizado de Máquina , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 637-640, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204910

RESUMO

OBJECTIVE: To explore the clinical features and therapeutic efficacy in adult ALL patients with t (1; 19) (E2A-PBX1). METHODS: The clinic data of 19 adult ALL patients with t (1; 19) (E2A-PBX1) in our hospital from Nov. 22, 2010 to Apr. 4, 2018 were collected. The clinical features,complete remission (CR) rate, overall survival (OS) rate and relapse-free survival (RFS) rate of patients received chemotherapy and chemotherapy+HSCT were analyzed. RESULTS: In all the 19 patients, the median age was 24 (14-66), median WBC count was 16.47×109 (1.8-170.34)/L, median Hb level was 98 (65-176) g/L, median Plt count was 50 (15-254)×109/L. Pre B-ALL were 17 cases (89.5%), and common B-ALL were 2 cases (10.5%). Patients received the induction therapy, the overall CR rate was 94.7%, one course CR rate was 94.7%, 4 year OS rate was 47.1% and RFS rate was 43.3%. The OS rate and RFS rate of patients received transplantation were slightly higher than those of patients not received transplantation (OS: 62.5% vs 36.7%) (P=0.188);RFS (62.5% vs 38.9%) (P=0.166). CONCLUSION: Most adult ALL patients with t (1; 19) (E2A-PBX1) is Pre B-ALL by Immunophenotyping, as compared with the pediatric patients, the therapeutic efficacy for adult patients with t (1; 19) (E2A-PBX1) is worsen, therefore, stem cell transplantation is still acquired for better long term survival.


Assuntos
Proteínas de Homeodomínio/genética , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Cromossomos Humanos Par 1 , Cromossomos Humanos Par 19 , Humanos , Imunofenotipagem , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Indução de Remissão
15.
Nat Immunol ; 20(7): 902-914, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31209404

RESUMO

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.


Assuntos
Rim/imunologia , Nefrite Lúpica/imunologia , Biomarcadores , Biópsia , Análise por Conglomerados , Biologia Computacional/métodos , Células Epiteliais/metabolismo , Citometria de Fluxo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imunofenotipagem , Interferons/metabolismo , Rim/metabolismo , Rim/patologia , Leucócitos/imunologia , Leucócitos/metabolismo , Nefrite Lúpica/genética , Nefrite Lúpica/metabolismo , Nefrite Lúpica/patologia , Linfócitos/imunologia , Linfócitos/metabolismo , Anotação de Sequência Molecular , Células Mieloides/imunologia , Células Mieloides/metabolismo , Análise de Célula Única , Transcriptoma
16.
Ann Hematol ; 98(8): 1845-1854, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31154474

RESUMO

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39+ Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39+ Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4+CD25+ Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4+CD25- Teff and CD4+CD25+ Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4+CD25- Teff cells had higher A2AR expression while CD4+CD25+ Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39+ Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4+CD25+ Treg cells and CD4+CD25- Teff cells. CD4+CD25- Teff cells had increased A2AR expression after treatment.


Assuntos
Apirase/genética , Dexametasona/uso terapêutico , Imunossupressores/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Receptor A2A de Adenosina/genética , Linfócitos T Reguladores/efeitos dos fármacos , Adenosina/imunologia , Adenosina/metabolismo , Trifosfato de Adenosina/imunologia , Trifosfato de Adenosina/metabolismo , Adulto , Idoso , Apirase/imunologia , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Imunofenotipagem , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/enzimologia , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/imunologia , Receptor A2A de Adenosina/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/enzimologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Reguladores/enzimologia , Linfócitos T Reguladores/imunologia
17.
Oncology ; 97(3): 135-148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31216557

RESUMO

BACKGROUND: We have developed a Wilms' tumor 1 (WT1)-targeting dendritic cell (DC)-based cancer vaccine combined with standard chemotherapy for patients with advanced pancreatic ductal adenocarcinoma (PDA). METHODS: We evaluated predictive markers of overall survival (OS) in PDA patients treated with multiple major histocompatibility complex class I/II-restricted, WT1 peptide-pulsed DC vaccinations (DC/WT1-I/II) in combination with chemotherapy. Throughout the entire period of immunochemotherapy, the plasma levels of soluble factors derived from granulocytes of 7 eligible PDA patients were examined. Moreover, systemic inflammatory response markers (neutrophil-to-lymphocyte ratio [NLR], monocyte-to-lymphocyte ratio [MLR], and granulocyte-to-lymphocyte ratio [GLR]) were assessed. In addition, cytoplasmic WT1 expression in PDA cells was examined. RESULTS: Compared to the 4 non-super-responders (OS <1 year), the remaining 3 super-responders (OS ≥1 year) showed significantly decreased low plasma matrix metalloproteinase-9 levels throughout long-term therapy. The NLR, MLR, and GLR after 5 DC/WT1-I/II vaccinations and 3 cycles of gemcitabine were significantly lower in the super-responders than in the non-super-responders. Furthermore, the cytoplasmic WT1 expression in the PDA cells of super-responders was relatively weak compared to that in the PDA cells of non-super-responders. CONCLUSIONS: Prolonged low levels of a granulocyte-related systemic inflammatory response after the early period of therapy and low cytoplasmic WT1 expression in PDA cells may be markers predictive of OS in PDA patients receiving WT1-targeting immunochemotherapy.


Assuntos
Biomarcadores Tumorais , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Imunoterapia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/mortalidade , Proteínas WT1/imunologia , Biomarcadores , Vacinas Anticâncer/administração & dosagem , Terapia Combinada , Células Dendríticas/metabolismo , Epitopos/imunologia , Feminino , Humanos , Imunofenotipagem , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/terapia , Peptídeos/imunologia , Peroxidase/metabolismo , Prognóstico , Fator de Crescimento Transformador beta1/metabolismo , Resultado do Tratamento , Vacinação , Proteínas WT1/genética
18.
Int Arch Allergy Immunol ; 180(1): 1-9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31242493

RESUMO

BACKGROUND: An inverse relation between Helicobacter pylori infection and asthma has been shown in epidemiological studies. Infection with H. pylori, or application of an extract of it before or after sensitization, inhibits allergic airway disease in mice. OBJECTIVES: The aim of this study was to investigate the effect of an extract of H. pylori on allergic airway disease induced by repeated allergen exposure in mice that were sensitized and challenged prior to extract application. METHOD: C57BL/6 mice were intranasally (i.n.) sensitized and challenged with house dust mite (HDM). After a minimum of 4 weeks, mice received the H. pylori extract intraperitoneally and were rechallenged i.n. with HDM. Allergen-specific antibodies were measured by ELISA. Cells present in the bronchoalveolar lavage fluid and dendritic cell (DC) subsets in the lung tissue were analyzed by flow cytometry. Tissue inflammation and goblet cell hyperplasia were assessed by histology. Cells of the mediastinal lymph node (mLN) were isolated and in vitro restimulated with HDM or H. pylori extract. RESULTS: Treatment with H. pylori extract before rechallenge reduced allergen-specific IgE, the DC numbers in the tissue, and goblet cell hyperplasia. Cells isolated from mLN of mice treated with the extract produced significantly more IL-10 and IL-17 after in vitro restimulation with HDM. mLN cells of H. pylori-treated mice that were re-exposed to the H. pylori extract produced significantly more interferon gamma. CONCLUSIONS: An extract of H. pylori is effective in reducing mucus production and various features of inflammation in HDM rechallenged mice.


Assuntos
Alérgenos/imunologia , Antígenos de Bactérias/imunologia , Células Caliciformes/patologia , Infecções por Helicobacter/complicações , Infecções por Helicobacter/imunologia , Helicobacter pylori/imunologia , Hipersensibilidade Respiratória/imunologia , Hipersensibilidade Respiratória/patologia , Animais , Biomarcadores , Biópsia , Citocinas/metabolismo , Exposição Ambiental , Feminino , Infecções por Helicobacter/microbiologia , Hiperplasia , Imunoglobulina E/imunologia , Imunoglobulina G/imunologia , Imunofenotipagem , Camundongos , Pyroglyphidae/imunologia
19.
Zhonghua Xue Ye Xue Za Zhi ; 40(4): 288-293, 2019 Apr 14.
Artigo em Chinês | MEDLINE | ID: mdl-31104439

RESUMO

Objective: To investigate the application values of immunophenotypic analysis and molecular genetics in the diagnosis of acute promyelocytic leukemia (APL) . Methods: The retrospective analyses of flow cytometric (FCM) immunophenotypic anyalysis, chromosome karyotype and chromosome fluorescence in situ hybridization (FISH) of 798 outpatient or hospitalization APL patients referred to our hospital between May 2012 and December 2017 were performed to further study the application values of FCM and molecular genetics in the diagnosis of APL. Results: The sensitivity and specificity of FCM were 91.9% and 98.7% respectively. The typical characteristic immunophenotype for APL was as of follows: a high SSC, absence of expression of cluster differntiation (CD) CD34 and HLA-DR, and expression or stronger expression of CD33, consistent expression of CD13, CD9, CD123, expression of CD56, CD7, CD2 (sometimes) . The rest 10% of the cases harbored atypical APL phenotypes, generally accompanied by CD34 and/or HLA-DR expression, decreased SSC and often accompanied by CD2 expression, it was difficult to definitively diagnose APL by this FCM phenotype, and their diagnoses depended on the results of genetics or molecular biology tests. Compared with normal individuals, complex karyotypes APL with t (15;17) translocation, other variant translocations and variant t (11;17) , t (5;17) had no significant differences in terms of their FCM phenotypes. Conclusions: FCM could rapidly and effectively diagnose APL. Despite the fact that complex karyotypes with various additional chromosomal abnormalities were detected in approximately one third of APL cases in addition to the pathognomonic t (15;17) (q22;q21) , they had no observable impact on the overall immunophenotype. Molecular and genetic criteria were the golden criteria for the diagnosis of APL. About 10% of immunophenotyping cases relied on molecular genetics for diagnosis.


Assuntos
Leucemia Promielocítica Aguda , Citometria de Fluxo , Humanos , Imunofenotipagem , Hibridização in Situ Fluorescente , Leucemia Promielocítica Aguda/diagnóstico , Estudos Retrospectivos
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