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1.
Scand J Immunol ; 86(6): 436-443, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28941312

RESUMO

Regulatory T cells (Tregs) represent a small subpopulation of CD4+ cells. Tregs are characterized by the expression of transcription factor Forkhead box protein 3 (FoxP3), also known as scurfin. Tregs are modulators of adaptive immune responses and play an important role in maintaining tolerance to self-antigens, providing the suppression associated with tumour microenvironment as well. These immunomodulatory properties are the main reason for the development of numerous therapeutic strategies, designed to inhibit the activity of cancer cells. However, due to Treg subpopulation diversity and its many functional pathways, the role of these cells in the cancer development and progression is still not fully understood.


Assuntos
Imunoterapia/métodos , Neoplasias/imunologia , Linfócitos T Reguladores/imunologia , Autoantígenos/imunologia , Vacinas Anticâncer , Fatores de Transcrição Forkhead/metabolismo , Humanos , Tolerância Imunológica , Imunomodulação , Masculino , Evasão Tumoral , Microambiente Tumoral
2.
Immunobiology ; 222(3): 499-505, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27773662

RESUMO

Tumors exert suppressive effects on the host immune system and tumor progression can be linked to functional impairments of immune cells. Regulatory T cells (Treg) are a subpopulation of T lymphocytes and play a key role in suppressing immune responses against autoimmune diseases and cancer. The aim of the study was to investigate the prevalence of Treg in malignant and benign pleural effusions and to evaluate the relationship between Treg frequency and disease advance. Pleural effusions from 76 patients were subjected to a routine laboratory diagnosis and analyzed by conventional cytology. Biological materials were divided into three groups: malignant pleural effusions with malignant cells, effusions from patients with malignancy but without malignant cells, and non-malignant pleural effusions. The frequency of Treg in malignant pleural effusions was significantly higher compared to non-malignant effusions. In general, the increase in Treg frequency was correlated with a decrease in the percentage of lymphocytes and an increase in T CD4+ and T CD4+ CD25+ cells. The highest percentage of Treg was observed among patients with the most advanced clinical stage of lung cancer in terms of size and location of a primary tumor, T4. A Kaplan-Meier survival analysis showed a statistically significant trend towards an adverse outcome for patients representing higher Treg counts. Overall, our results support the extraordinary potential of Treg control in future anticancer therapy.


Assuntos
Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Derrame Pleural Maligno/imunologia , Derrame Pleural Maligno/patologia , Linfócitos T Reguladores/imunologia , Biomarcadores , Progressão da Doença , Feminino , Humanos , Imunofenotipagem , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Contagem de Linfócitos , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Carga Tumoral
3.
Scand J Immunol ; 81(1): 2-10, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25359529

RESUMO

Many different cells produce and release membraneous microvesicles (MV) or exosomes into their microenvironment. Exosomes represent a specific subtype of secreted derived vesicles which are defined as homogenous vesicles of 30-100 nm lined by a lipid bilayer, which contain a specific set of proteins, lipids, and nucleic acids. There are clear evidences that they serve as important biological signals messengers and carriers in physiological as well as in pathological processes. Those derived from tumours (tumour-derived exosomes, TD-exosomes) function as protumourigenic factors that can mediate intercellular communication in the tumour microenvironment and also contribute to cancer progression. The main functions of exosomes in the cancer microenvironment include the following: promotion of primary cancer growth, stimulation of angiogenesis, activation of stromal fibroblasts, sculpting the cancer ECM, generation of a premetastatic niche and suppression of host immune response. Exosomes have recently emerged as potentially promising diagnostic and prognostic biomarkers in cancer and other diseases. This article is a summary of information about the structure and origin of exosomes and also indicates the importance of exosomes and microRNAs in lung cancer. The role of exosomes in NSCLC is little known, and its explanation requires thorough research.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Exossomos , Neoplasias Pulmonares/patologia , Microambiente Tumoral , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Comunicação Celular , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Exossomos/química , Exossomos/genética , Exossomos/metabolismo , Humanos , Lipídeos/análise , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , Corpos Multivesiculares/metabolismo , Neovascularização Patológica/patologia
4.
Scand J Immunol ; 80(2): 75-84, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24845558

RESUMO

It is widely accepted that type 1 diabetes mellitus (T1DM) is an autoimmune disease resulting from an interaction between immunologic, genetic and environmental factors. However, the exact mechanism leading to the development of T1DM remains incomplete. There is a large body of evidence pointing towards the important role of toll-like receptor (TLR) activation and vitamin D deficiency in T1DM pathogenesis. In this article, we review the available data on the influence of TLRs' level of activation and vitamin D status on the risk of the development of T1DM in humans and rodent models. We also summarize the current information regarding the interactions between TLRs' level of activation, vitamin D status and various environmental factors, such as enteroviral infections, the gut microbiota and breastfeeding substitution, among others. Our results stipulate that vitamin D seems to protect against T1DM by reducing the TLRs' level of activation.


Assuntos
Diabetes Mellitus Tipo 1/genética , Receptores Toll-Like/imunologia , Deficiência de Vitamina D/metabolismo , Vitamina D/imunologia , Animais , Linfócitos T CD8-Positivos/imunologia , Diabetes Mellitus Tipo 1/epidemiologia , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Camundongos , Ratos , Receptores de Calcitriol/imunologia , Receptores Toll-Like/biossíntese , Vitamina D/metabolismo
5.
J Physiol Pharmacol ; 59 Suppl 6: 321-30, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19218656

RESUMO

Malignant tumors contain numerous macrophages as a major component of the leukocytic infiltrate. Only few studies have evaluated the interaction between products secreted by macrophages and tumor cells. Our objective was to study soluble factors produced by pleural macrophages. We sampled pleural effusions from patients with cancer and used human tumor cell lines as targets. Pleural macrophages were cultured and the supernatants were used as a conditioned medium for cultures of human cell lines A549, HT29, HCT116, SW620, MCF7, MDA-MB231, JURKAT, and HL60. We investigated apoptosis, proliferative activity, and expression of apoptosis regulating proteins Fas, Bcl2, Caspase-3, and survivin of malignant cells cultured in the conditioned medium. Our findings raise the possibility that macrophages from malignant pleural effusions can act as a factor inhibiting apoptosis of malignant cells.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Macrófagos/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Pleura/patologia , Animais , Anexina A5/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Meios de Cultivo Condicionados , Citometria de Fluxo , Corantes Fluorescentes , Humanos , Marcação In Situ das Extremidades Cortadas , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Neoplasias/imunologia , Derrame Pleural/patologia
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