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3.
J Cancer Res Clin Oncol ; 145(10): 2541-2546, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31367835

RESUMO

BACKGROUND: The neutrophil to lymphocyte ratio (NLR) is known to be prognostic for patients with advanced cancers treated with immune checkpoint inhibitors (ICI), but has generally been evaluated as a single threshold value at baseline. We evaluated NLR at baseline and within first month during treatment in patients who received ICI for advanced cancer to evaluate the prognostic value of baseline and of changes from baseline to on-treatment NLR. METHODS: A retrospective review of patients with advanced cancer treated with ICI from 2011 to 2017 at the Ohio State University was performed. NLR was calculated at the initiation of ICI and repeated at median of 21 days. Overall survival (OS) was calculated from the initiation of ICI to date of death or censored at last follow-up. Significance of Cox proportional hazards models were evaluated by log-rank test. Calculations were performed using the survival and survminer packages in R, and SPSS. RESULTS: 509 patients were identified and included in the analysis. Patients with baseline and on-treatment NLR < 5 had significantly longer OS (P < 0.001). The change in NLR overtime was a predictor of OS and was observed to be non-linear in nature. This property remained statistically significant with P < 0.05 after adjusting for age, body mass index, sex, cancer type, performance status, and days to repeat NLR measurement. Patients with a moderate decrease in NLR from baseline had the longest OS of 27.8 months (95% CI 21.8-33.8). Patients with significant NLR decrease had OS of 11.4 months (95% CI 6.1-16.7). Patients with a significant increase in NLR had the shortest OS of 5.0 months (95% CI 0.9-9.1). CONCLUSIONS: We confirmed the prognostic value of NLR in patients with advanced cancer treated with ICIs. We found that change in NLR over time is a non-linear predictor of patient outcomes. Patients who had moderate decrease in NLR during treatment with ICI were found to have the longest survival, whereas a significant decrease or increase in NLR was associated with shorter survival. To our knowledge, this is the first study to demonstrate a non-linear change in NLR over time that correlates with survival.


Assuntos
Contagem de Leucócitos , Contagem de Linfócitos , Linfócitos , Neoplasias/sangue , Neoplasias/mortalidade , Neutrófilos , Adulto , Idoso , Biomarcadores , Feminino , Humanos , Imunoterapia , Estimativa de Kaplan-Meier , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/terapia , Neutrófilos/imunologia , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
4.
Cancer Invest ; 37(6): 265-274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31304800

RESUMO

A meta-analysis of 14 studies (16 cohorts) incorporating 1751 participants was performed to evaluate the correlation between baseline neutrophil-to-lymphocyte ratio (NLR) and outcome of immune checkpoint inhibitors (ICI). The pooled hazard ratio (HR) suggested elevated pretreatment NLR was associated with poor OS (HR: 2.61, 95% confidence intervals (CI): 1.77-3.86, p < 0.00001) and PFS (HR: 1.74, 95% CI: 1.34-2.27, p < 0.0001). Stratified analyses on tumor types, ICI agents, the cutoff value of NLR and study regions exhibited the similar outcomes. This study demonstrated that elevated NLR was a predictor of poor OS and PFS for ICI.


Assuntos
Antineoplásicos/imunologia , Antineoplásicos/uso terapêutico , Linfócitos/imunologia , Neutrófilos/imunologia , Feminino , Humanos , Imunoterapia/métodos , Contagem de Linfócitos , Linfócitos/efeitos dos fármacos , Masculino , Neutrófilos/efeitos dos fármacos , Prognóstico
5.
Exp Parasitol ; 204: 107725, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31306646

RESUMO

Characterisation of the cellular immune response to schistosomiasis is well established for Schistosoma mansoni but a comprehensive description of T cell-mediated immune responses against S. japonicum infection is lacking. Accordingly, 20 CBA mice were infected with cercariae of S. japonicum and the immune response at different time points was determined. Mouse spleen and liver lymphocytes were isolated from the mice and stimulated with schistosomal adult worm antigen preparation (SWAP) and schistosomal soluble egg antigen (SEA). There was a relatively higher Th1 immune response to SWAP compared to SEA at the early phase of infection (up to week 5 post challenge). However, a Th2 immune response directed against SEA was dominant at week 6 post-infection, a time point when the highest IgG response against both SWAP and, especially, SEA was generated. The regulatory immune response was highest at the early phase of the immune response (up to week 5 post challenge) followed by a rapid decline at week 6-post infection. Before egg-laying, S. japonicum induced a regulatory T cell immune response which may limit the early Th1-mediated immune response that is believed to be protective in murine schistosomiasis. Following egg laying, the immune response was polarized to a Th2 immune response mainly directed against the eggs and this may contribute to parasite survival.


Assuntos
Imunidade Celular , Schistosoma japonicum/imunologia , Esquistossomose Japônica/imunologia , Linfócitos T/imunologia , Animais , Antígenos de Helmintos/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Interleucina-17/imunologia , Interleucina-17/metabolismo , Fígado/citologia , Fígado/imunologia , Fígado/parasitologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos CBA , Óvulo/imunologia , Contagem de Ovos de Parasitas , Receptores de Antígenos de Linfócitos T gama-delta/imunologia , Caramujos/parasitologia , Baço/citologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th2/imunologia
6.
Nat Commun ; 10(1): 2712, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221971

RESUMO

Clostridium difficile (C. difficile) incidence has tripled over the past 15 years and is attributed to the emergence of hypervirulent strains. While it is clear that C. difficile toxins cause damaging colonic inflammation, the immune mechanisms protecting from tissue damage require further investigation. Through a transcriptome analysis, we identify IL-33 as an immune target upregulated in response to hypervirulent C. difficile. We demonstrate that IL-33 prevents C. difficile-associated mortality and epithelial disruption independently of bacterial burden or toxin expression. IL-33 drives colonic group 2 innate lymphoid cell (ILC2) activation during infection and IL-33 activated ILC2s are sufficient to prevent disease. Furthermore, intestinal IL-33 expression is regulated by the microbiota as fecal microbiota transplantation (FMT) rescues antibiotic-associated depletion of IL-33. Lastly, dysregulated IL-33 signaling via the decoy receptor, sST2, predicts C. difficile-associated mortality in human patients. Thus, IL-33 signaling to ILC2s is an important mechanism of defense from C. difficile colitis.


Assuntos
Clostridium difficile/imunologia , Enterocolite Pseudomembranosa/imunologia , Imunidade Inata , Interleucina-33/metabolismo , Linfócitos/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antibacterianos/efeitos adversos , Toxinas Bacterianas/imunologia , Toxinas Bacterianas/metabolismo , Clostridium difficile/patogenicidade , Colo/citologia , Colo/imunologia , Colo/microbiologia , Colo/patologia , Modelos Animais de Doenças , Enterocolite Pseudomembranosa/microbiologia , Enterocolite Pseudomembranosa/mortalidade , Enterocolite Pseudomembranosa/terapia , Transplante de Microbiota Fecal , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/imunologia , Perfilação da Expressão Gênica , Humanos , Interleucina-33/imunologia , Linfócitos/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia , Virulência/imunologia , Adulto Jovem
7.
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
8.
Transplant Proc ; 51(4): 1016-1020, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31101162

RESUMO

AIM: Antibody assessment during pretransplantation term is important to detect donor specific antibodies. These donor-specific antibodies are determined by various crossmatch methods (flow cytometric [FCXM], complement-dependent cytotoxic [CDCXM], and Luminex [LMXM]). Recently, single antigen bead (SAB) assays have been used for the assessment of hypersensitized patients. The aim of this study was to compare sensitivity and specificity of the 3 crossmatch methods in reference to the SAB method. METHOD: In this study, 69 hypersensitized patients with high class I and/or class II panel reactive antibodies were tested using the flow cytometric SAB method. Serum samples were cross-matched by 3 crossmatch methods with the cells of a volunteer healthy individual, and the results were evaluated according to HLA and cross-reactive epitope groups (CREGs). RESULTS: Sensitivity was found to be better with T FCXM (0.91) and class I LMXM (0.87). Specificity of peripheral blood lymphocyte CDCXM method (1.0) was found to be better than the other 2 methods (0.33 and 0.57, respectively). Sensitivity of class II LMXM (0.88) was found to be better than the others (0.42 for B CDCXM and 0.82 for B FCXM, respectively). The specificity of the B CDCXM, B FCXM, and class II LMXM was similar (0.44, 0.44, and 0.33, respectively). CREGs results were similar to HLA results. CONCLUSION: Although CDCXM has high specificity for the detection of anti-HLA antibodies, it has low sensitivity. To increase sensitivity, FCXM or LMXM methods may be used with the CDCXM test. These results will be beneficial for laboratories and clinicians during graft survival and patient health assessment.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas/métodos , Isoanticorpos/análise , Adulto , Feminino , Citometria de Fluxo/métodos , Antígenos HLA/imunologia , Humanos , Linfócitos/imunologia , Pessoa de Meia-Idade , Sensibilidade e Especificidade
9.
Microb Pathog ; 133: 103560, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31145981

RESUMO

Toxoplasma gondii is an intracellular zoonotic parasite that causes toxoplasmosis, which can cause economic losses and serious public health problems worldwide. A member of the T. gondii calcium-dependent protein kinases family, TgCDPK1 was recently identified as an essential regulator of exocytosis in T. gondii, and participated in direct parasite motility, host-cell invasion and egress. In the present study, the protective immunity of recombinant TgCDPK1 protein (rTgCDPK1) was evaluated against acute toxoplasmosis in mice. rTgCDPK1 were expressed and purified, BABL/c mice were intraperitoneally immunized with rTgCDPK1 and challenged with the highly virulent RH strain of T. gondii. The specific immune responses were analyzed by measuring the cytokine and serum antibody, and lymphocyte proliferation assays, flow cytometry of lymphocytes and the survival curve were employed to evaluate the protective efficacy. From the results we found that special humoral and cellular responses could be elicited in vaccine mice, and higher level of IgG antibody, and the significant increased levels of Th1-type cytokines IFN-γ, IL-12 (p70), IL10 and CD3+CD4+CD8- and CD3+CD8+CD4- T cells could also be detected comparing to control mice (P < 0.05). All vaccinated mice prolonged survival time (14.90 ±â€¯2.89 days) challenge with 1000 tachyzoites of RH, while the control mice died within 8 days. These results indicated that TgCDPK1 protein was a potential vaccine candidate against acute toxoplasmosis.


Assuntos
Imunização , Proteínas Quinases/genética , Proteínas Quinases/imunologia , Toxoplasma/imunologia , Toxoplasmose Animal/prevenção & controle , Animais , Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/genética , Antígenos de Protozoários/imunologia , Clonagem Molecular , Citocinas/metabolismo , Feminino , Genes de Protozoários/genética , Imunidade Celular , Imunidade Humoral , Imunoglobulina G/sangue , Linfócitos/imunologia , Camundongos , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Baço/imunologia , Análise de Sobrevida , Toxoplasma/genética , Toxoplasmose Animal/imunologia , Vacinas de DNA/imunologia
10.
Int J Mol Sci ; 20(9)2019 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-31072011

RESUMO

Group 2 innate lymphoid cells (ILC2) have emerged as a major component of type 2 inflammation in mice and humans. ILC2 secrete large amounts of interleukins 5 and 13, which are largely responsible for host protective immunity against helminth parasites because these cytokines induce profound changes in host physiology that include: goblet cell metaplasia, mucus accumulation, smooth muscle hypercontractility, eosinophil and mast cell recruitment, and alternative macrophage activation (M2). This review covers the initial recognition of ILC2 as a distinct cell lineage, the key studies that established their biological importance, particularly in helminth infection, and the new directions that are likely to be the focus of emerging work that further explores this unique cell population in the context of health and disease.


Assuntos
Helmintíase/imunologia , Helmintos/imunologia , Imunidade Inata/imunologia , Linfócitos/imunologia , Animais , Linhagem da Célula/imunologia , Helmintíase/parasitologia , Helmintos/patogenicidade , Humanos , Imunidade Inata/genética , Interleucina-13/genética , Interleucina-5/genética , Camundongos
11.
Parasit Vectors ; 12(1): 249, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113489

RESUMO

BACKGROUND: Whirling disease (WD), caused by the myxozoan parasite Myxobolus cerebralis, is responsible for high mortalities in rainbow trout hatcheries and natural populations. To elucidate how resistant and susceptible rainbow trout strains respond to early invasion, a well-established model of WD was used to demonstrate the kinetics of local and systemic immune responses in two rainbow trout strains, the susceptible American Trout Lodge (TL) and the more resistant German Hofer strain (HO). METHODS: Parasite load and cellular immune responses were compared across several time points after M. cerebralis exposure to elucidate the kinetics of immune cells in resistant and susceptible rainbow trout in response to early invasion. In the course of the 20 days following exposure, leukocyte kinetics was monitored by flow cytometry in the caudal fin (CF), head kidney (HK) and spleen (SP). For the analysis of the leukocyte composition, cells were stained using a set of monoclonal antibodies with known specificity for distinct subpopulations of rainbow trout leukocytes. RESULTS: Experiments indicated general increases of CF, HK and SP myeloid cells, while decreases of B cells and T cells in the SP and HK were observed at several time points in the TL strain. On the other hand, in the HO strain, increases of T cells were dominant in CF, HK and SP at multiple time points. The differences between HO and TL were most distinct at 2, 4, 12 and 48 hours post-exposure (hpe) as well as at 4 days post-exposure (dpe), with the vast majority of innate immune response cells having higher values in the susceptible TL strain. Alteration of the leukocyte populations with augmented local cellular responses and excessive immune reactions likely lead to subsequent host tissue damage and supports parasite invasion and development in TL. CONCLUSIONS: The findings of this study highlight the significance of effective local and systemic immune reaction and indicate proper activation of T lymphocytes critical for host resistance during M. cerebralis infection. The present study provides insights into the cellular basis of protective immune responses against M. cerebralis and can help us to elucidate the mechanisms underlying the variation in resistance to WD.


Assuntos
Suscetibilidade a Doenças , Doenças dos Peixes/imunologia , Linfócitos/imunologia , Oncorhynchus mykiss/parasitologia , Doenças Parasitárias em Animais/imunologia , Animais , Linfócitos B/imunologia , Modelos Animais de Doenças , Imunidade Celular , Imunidade Inata , Cinética , Myxobolus/imunologia , Carga Parasitária , Infecções por Protozoários/imunologia , Linfócitos T/imunologia
12.
Methods Mol Biol ; 1979: 305-315, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31028646

RESUMO

Flow cytometry is one of the most suitable techniques for analyzing and classifying different cell suspensions derived from blood or others compartments. The characterization of all different cellular subtypes is made with different antibodies that detect surface or intracytoplasmic antigens. Here we describe the technique to thoroughly characterize immune cells from tumor infiltrates and proceed to isolation using single-cell sorting.


Assuntos
Citometria de Fluxo/métodos , Leucócitos/imunologia , Neoplasias/imunologia , Análise de Célula Única/métodos , Animais , Antígenos CD/análise , Antígenos CD/imunologia , Humanos , Leucócitos/patologia , Linfócitos/imunologia , Linfócitos/patologia , Camundongos , Monócitos/imunologia , Monócitos/patologia , Neoplasias/patologia , Ratos , Coloração e Rotulagem/métodos
13.
Bull Exp Biol Med ; 166(6): 714-718, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31020580

RESUMO

Specific features of neurological deficit and changes in the cellular composition of tracheal lymphoid structures during the immediate stage (day 1) of hemorrhagic stroke were studied in rats with various behavioral parameters. Modeling of hemorrhage in the left caudate nucleus of the brain was followed by the development of motor disturbances in the forelimb use asymmetry test and corner rotation paradigm. These animals preferred to use the left forelimb (ipsilateral to the side of hemorrhage) to lean on the cylinder wall. The frequency of using the right forelimb or both forelimbs was reduced under these conditions. The number of left-sided rotations increased, while the percentage of right-sided rotations decreased. The observed changes were accompanied by immune dysfunction. It was manifested in the depletion of lymphoid aggregates of the tracheal wall in lymphocytes and plasma cells. The severity of abnormal neurological symptoms and disturbances in immune homeostasis during the immediate stage of hemorrhagic stroke was greater in behaviorally passive rats than in active specimens.


Assuntos
Núcleo Caudado/fisiopatologia , Hemorragia Cerebral/fisiopatologia , Tecido Linfoide/fisiopatologia , Acidente Vascular Cerebral/fisiopatologia , Traqueia/fisiopatologia , Animais , Comportamento Animal , Núcleo Caudado/imunologia , Núcleo Caudado/patologia , Hemorragia Cerebral/imunologia , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Lateralidade Funcional , Imunidade Inata , Contagem de Linfócitos , Linfócitos/imunologia , Linfócitos/patologia , Tecido Linfoide/imunologia , Tecido Linfoide/patologia , Masculino , Atividade Motora , Ratos , Ratos Wistar , Acidente Vascular Cerebral/imunologia , Acidente Vascular Cerebral/patologia , Traqueia/imunologia , Traqueia/patologia
14.
Immunity ; 50(4): 778-795, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30995499

RESUMO

Forty years after its naming, interleukin-1 (IL-1) is experiencing a renaissance brought on by the growing understanding of its context-dependent roles and advances in the clinic. Recent studies have identified important roles for members of the IL-1 family-IL-18, IL-33, IL-36, IL-37, and IL-38-in inflammation and immunity. Here, we review the complex functions of IL-1 family members in the orchestration of innate and adaptive immune responses and their diversity and plasticity. We discuss the varied roles of IL-1 family members in immune homeostasis and their contribution to pathologies, including autoimmunity and auto-inflammation, dysmetabolism, cardiovascular disorders, and cancer. The trans-disease therapeutic activity of anti-IL-1 strategies argues for immunity and inflammation as a metanarrative of modern medicine.


Assuntos
Imunidade Adaptativa/imunologia , Citocinas/fisiologia , Imunidade Inata/imunologia , Inflamação/imunologia , Interleucina-1/fisiologia , Animais , Doenças Cardiovasculares/imunologia , Citocinas/genética , Citocinas/imunologia , Gastroenteropatias/imunologia , Hematopoese/imunologia , Humanos , Interleucina-1/imunologia , Linfócitos/imunologia , Camundongos , Camundongos Knockout , Família Multigênica , Neoplasias/imunologia , Doenças Neurodegenerativas/imunologia , Receptores de Citocinas/genética , Receptores de Citocinas/imunologia
15.
Int J Mol Sci ; 20(7)2019 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-30965592

RESUMO

Mast cells play a critical role in the pathogenesis of allergic asthma. Histamine is a central mediator released from mast cells through allergic reactions. Histamine plays a role in airway obstruction via smooth muscle contraction, bronchial secretion, and airway mucosal edema. However, previous clinical trials of H1 receptor antagonists (H1RAs) as a treatment for asthma were not successful. In recent years, type 2 innate immunity has been demonstrated to be involved in allergic airway inflammation. Allergic asthma is defined by IgE antibody-mediated mast cell degranulation, while group 2 innate lymphoid cells (ILC2) induce eosinophilic inflammation in nonallergic asthma without allergen-specific IgE. Anti-IgE therapy has demonstrated prominent efficacy in the treatment of severe allergic asthmatics sensitized with specific perennial allergens. Furthermore, recent trials of specific cytokine antagonists indicated that these antagonists were effective in only some subtypes of asthma. Accordingly, H1RAs may show significant clinical efficacy for some subtypes of allergic asthma in which histamine is deeply associated with the pathophysiology.


Assuntos
Asma/metabolismo , Asma/fisiopatologia , Histamina/metabolismo , Animais , Antagonistas dos Receptores Histamínicos/uso terapêutico , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Humanos , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Linfócitos/metabolismo , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo
16.
Int J Immunopathol Pharmacol ; 33: 2058738419839592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30968711

RESUMO

A better understanding of the immune profile of non-small cell lung cancer (NSCLC) and the immunomodulatory impact of chemotherapy is essential to develop current therapeutic approaches. Herein, we collected peripheral blood from 20 healthy donors and 50 patients with advanced NSCLC, before and after chemotherapy, followed by phenotypic analysis of lymphocyte subsets and assessment of the correlation between their post-chemotherapy levels and progression-free survival (PFS). Results showed that, before chemotherapy, the levels of CD8+ lymphocytes, PD-1+CD4+, Th2, and Th17 cells were elevated in patients' peripheral blood, in contrast to natural killer (NK) cells and Th1 cells. Besides, there was no remarkable difference in the frequency of PD-1+CD8+ cells between patients and healthy controls. After chemotherapy, the levels of CD8+ lymphocytes, NK, Th2, Th17, and Treg were declined, in contrast to the level of Th1 cells which was markedly increased. Importantly, chemotherapy had no impact on the frequencies of PD-1+CD8+ and PD-1+CD4+ cells. PFS was significantly better in patients with low percentage of PD-1+CD4+ T cells than those with high percentage. Patients with high content of Th1 cells showed longer PFS than those with low content. The low percentages of Th17 and Treg cells were correlated with longer PFS, even though the difference did not reach statistical significance. In conclusion, the imbalance of lymphocyte subsets is a hallmark of NSCLC. Furthermore, the high level of PD-1+CD4+ cells plays a crucial role in the progression of NSCLC and could be used as a prognostic marker; and the high level of Th1 could predict better clinical outcomes of chemotherapy.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Fatores Imunológicos/uso terapêutico , Neoplasias Pulmonares/imunologia , Linfócitos/imunologia , Idoso , Antineoplásicos Imunológicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/imunologia , Feminino , Humanos , Fatores Imunológicos/farmacologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/tratamento farmacológico , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida/tendências , Resultado do Tratamento
17.
Microb Pathog ; 131: 254-258, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30999020

RESUMO

BACKGROUND: Canine distemper virus (CDV) can cause a highly contagious disease to canid. However, how CDV affects peripheral blood lymphocyte (PBL) remains unclear. METHODS: In this study, CDV infected PBL was cultured to investigate the effect of CDV on the differentiation of lymphocytes and the mRNA expression of inflammatory cytokines in PBL. RESULTS: The results showed that CDV changed the phenotype of lymphocytes and increased the percentage of CD4+CD8+ T cells. To explore the effect of immune response of lymphocytes to CDV, the mRNA expression of pro- and anti-inflammatory cytokines was examined. Interleukin (IL-6, IL-12B), and tumor necrosis factor (TNF)-α mRNA expression was significantly increased at 12-48 h after CDV infection. IL-10 mRNA expression was dramatically enhanced at 12-36 h after CDV infection. However, IL-4 and transforming growth factor (TGF-ß) were not response to CDV infection. These results indicated that PBL differentiated intoCD4+CD8+ T cells and improved the inflammatory response to CDV infection. CONCLUSIONS: After CDV infection, PBL differentiated into CD4+CD8+ T cells and initiated inflammatory response.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular , Citocinas/metabolismo , Vírus da Cinomose Canina/patogenicidade , Cinomose/imunologia , Linfócitos/metabolismo , RNA Mensageiro/metabolismo , Animais , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Cinomose/virologia , Cães , Feminino , Interleucina-10/metabolismo , Linfócitos/imunologia , Fenótipo , Fator de Crescimento Transformador beta/metabolismo
18.
Int J Mol Sci ; 20(8)2019 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-30999584

RESUMO

Innate lymphoid cells (ILCs) represent a heterogeneous population of recently discovered immune cells that mirror the functions of adaptive T lymphocytes. However, ILCs are devoid of specific antigen receptors and cellular activation depends on environmental cytokines, rendering them as early regulators of immune responses. Type 2 innate lymphoid cells (ILC2s) respond to alarmins, such as interleukin-25 and -33 and shape Th2-associated immunity by expressing IL-5 and IL-13 in a GATA3-dependent manner. In addition, ILC2s express the epidermal growth factor-like molecule Amphiregulin thereby promoting regeneration of injured tissue during inflammation. The gut and liver confer nutrient metabolism and bidirectional exchange of products, known as the gut-liver axis. Accordingly, both organs are continuously exposed to a large variety of harmless antigens. This requires avoidance of immunity, which is established by a tolerogenic environment in the gut and liver. However, dysregulations within the one organ are assumed to influence vitality of the other and frequently promote chronic inflammatory settings with poor prognosis. Intensive research within the last years has revealed that ILC2s are involved in acute and chronic inflammatory settings of gut and liver. Here, we highlight the roles of ILC2s in intestinal and hepatic inflammation and discuss a regulatory potential.


Assuntos
Inflamação/imunologia , Intestinos/imunologia , Fígado/imunologia , Ativação Linfocitária , Linfócitos/imunologia , Animais , Movimento Celular , Citocinas/imunologia , Humanos , Imunidade Inata , Intestinos/citologia , Fígado/citologia , Linfócitos/citologia
19.
Artigo em Inglês | MEDLINE | ID: mdl-30961815

RESUMO

Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease of unknown cause. In the study, we found that duck circovirus (DuCV) induces PSC in natural and reproductive cases. PSC in DuCV naturally infected ducks was investigated by PCR and histopathology. A model of PSC was developed in one-day old duck by infection of DuCV. Effects on serum levels of liver enzymes and histology were evaluated, and DuCV tropism for bile duct in liver was analyzed by immuohistochemistry. Pathology observation of natural or reproductive DuCV infected ducks showed that the lesion of liver were characterized by cholangiocytic injuries and progressive fibrous obliteration of the biliary tree associated with lymphocytes infiltration. ALT, AST, ALP, GGT, ALB, TBIL and TP were significantly increased in serum of DuCV infected ducks. DuCV showed higher tropism for epithelial cells of bile duct than other cells in PSC.


Assuntos
Ductos Biliares/virologia , Doenças das Aves/fisiopatologia , Colangite Esclerosante/fisiopatologia , Colangite Esclerosante/virologia , Circovirus/fisiologia , Tropismo Viral/fisiologia , Animais , Ductos Biliares/citologia , Doenças das Aves/virologia , Colangite Esclerosante/imunologia , Circovirus/imunologia , Patos , Humanos , Fígado/patologia , Fígado/virologia , Linfócitos/imunologia
20.
Anticancer Res ; 39(4): 2169-2176, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30952764

RESUMO

BACKGROUND/AIM: Recently, several systemic inflammation-based scores, such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), modified Glasgow prognostic score (GPS), and prognostic nutritional index (PNI), have been proposed as prognostic factors for several cancers. In this study, we aimed to determine the influence of systemic inflammation-based scores and nutrition status on the outcome in patients receiving chemotherapy for unresectable pancreatic cancer. PATIENTS AND METHODS: A total of 93 consecutive patients who underwent chemotherapy for unresectable pancreatic cancer at Osaka Medical College Hospital, Takatsuki, Japan, between January 2008 and December 2014 were eligible for this study. The outcomes assessment included one- and two-year overall survival (OS) rates, according to changes in LMR and PNI prior to, and following chemotherapy. RESULTS: LMR<3.4 (OR=5.02, 95%CI=1.559-19.85, p=0.005) and PNI<43 (OR=3.53, 95%CI=1.057-14.21, p=0.03) independently predicted a poor outcome in patients receiving chemotherapy for unresectable pancreatic cancer using multivariate analysis. According to changes in LMR and PNI prior to, and following chemotherapy, compared to patients who maintained LMR≥3.4, patients whose LMR decreased from ≥3.4 to <3.4 had significantly lower OS rates (p<0.001). Similarly, compared to patients who maintained PNI≥43, patients whose PNI deteriorated had significantly lower OS rates (56.2% versus 25.8% at one year, and 12.5% versus 0% at two years; p=0.003). CONCLUSION: LMR<3.4 and PNI<43 are identified as independent predictors of poor outcome in patients receiving chemotherapy for unresectable pancreatic cancer. LMR and PNI may help clinicians identify patients at high risk for poor prognosis.


Assuntos
Linfócitos/imunologia , Monócitos/imunologia , Avaliação Nutricional , Neoplasias Pancreáticas/imunologia , Idoso , Feminino , Humanos , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Prognóstico
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