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1.
Am J Case Rep ; 22: e925345, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495947

RESUMO

BACKGROUND Infliximab, a monoclonal antibody against tumor necrosis factor (TNF) alpha with proven efficacy and known safety profile, is currently widely used in the treatment of inflammatory bowel diseases. Increased risk for serious infections and malignant neoplasms secondary to immunosuppression is a major concern during therapy with this medication. Histoplasmosis is a granulomatous disease caused by the fungus Histoplasma capsulatum. Disseminated forms of the disease have immunodepression as a major risk factor. CASE REPORT A 39-years-old man had been followed with refractory fistulizing ileocolonic Crohn's disease using combination therapy (infliximab plus azathioprine) and also receiving short courses of steroids. After 2 years of this immunosuppressive therapy, the patient presented with high fever (39.5ºC) for 5 days, associated with profuse sweating, and moderate pain in the left hypochondrium. The patient was hospitalized. Diagnoses of tuberculosis, malignancy, autoimmune diseases, and bacterial and viral infections were rapidly discarded after investigation. Clinical, laboratory, and image signs of liver involvement prompted a guided percutaneous biopsy, which revealed granulomatous hepatitis, with the presence of fungal structures suggestive of Histoplasma capsulatum. Upon treatment with liposomal amphotericin followed by itraconazole, the patient showed an impressively positive clinical response. CONCLUSIONS TNF blockers, particularly when associated with other immunosuppressors, are a serious risk factor for opportunistic infections. This unusual case of disseminated histoplasmosis in a patient with Crohn's disease using infliximab in combination with azathioprine and steroids emphasizes the need for surveillance of this uncommon but potentially lethal complication before starting TNF blockers therapy.


Assuntos
Doença de Crohn , Histoplasmose , Adulto , Doença de Crohn/complicações , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Histoplasma , Histoplasmose/diagnóstico , Humanos , Imunossupressão , Infliximab/efeitos adversos , Masculino
2.
BMJ Case Rep ; 14(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376424

RESUMO

A 39-year-old man with diabetes mellitus and hypertension presented two years following renal transplantation with evening pyrexia, night sweats and loss of weight. He was diagnosed with disseminated tuberculosis and invasive aspergillosis and commenced on antituberculous and antifungal therapy. Immunosuppressants except for the maintenance dose of steroids were discontinued. Two weeks later, he acquired severe COVID-19 pneumonia complicated with type 1 respiratory failure and haemodynamic instability. He was treated with non-invasive ventilation and inotropic support with a vasopressor-augmenting dose of steroids. Management challenges were diagnosing the respiratory pathologies with limited investigations, deciding on continuation of steroids in an organ transplant recipient with disseminated infection and deciding the ceiling of care in a low-resource setting given the background of multiple pulmonary insults. A multidisciplinary team decided to continue high-dose steroids and escalate to a full ceiling of care. He recovered from COVID-19 pneumonia 15 days following diagnosis and was discharged home. The potential adverse effects of steroids on tuberculosis and aspergillosis are to be monitored during follow-up.


Assuntos
Aspergilose , COVID-19 , Transplante de Rim , Adulto , Aspergilose/diagnóstico , Aspergilose/tratamento farmacológico , Humanos , Imunossupressão/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , SARS-CoV-2
3.
Trends Parasitol ; 37(10): 859-862, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34364804

RESUMO

The clinical picture of the fungal disease, Pneumocystis pneumonia, resembles the course of coronavirus disease 2019 (COVID-19), presenting a diagnostic challenge in the pandemic era. We discuss the concern of Pneumocystis jirovecii and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coinfection, their similarities, and the impact of immunosuppression, with a suggested diagnostic pathway for their suspected coinfection.


Assuntos
COVID-19/diagnóstico , Imunossupressão , Pneumonia por Pneumocystis/diagnóstico , COVID-19/complicações , Coinfecção , Humanos , Pandemias , Pneumocystis carinii , Pneumonia por Pneumocystis/complicações
5.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34445343

RESUMO

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune central nervous system (CNS) inflammatory disorder that can lead to serious disability and mortality. Females are predominantly affected, including those within the reproductive age. Most patients develop relapsing attacks of optic neuritis; longitudinally extensive transverse myelitis; and encephalitis, especially brainstem encephalitis. The majority of NMOSD patients are seropositive for IgG autoantibodies against the water channel protein aquaporin-4 (AQP4-IgG), reflecting underlying aquaporin-4 autoimmunity. Histological findings of the affected CNS tissues of patients from in-vitro and in-vivo studies support that AQP4-IgG is directly pathogenic in NMOSD. It is believed that the binding of AQP4-IgG to CNS aquaporin-4 (abundantly expressed at the endfoot processes of astrocytes) triggers astrocytopathy and neuroinflammation, resulting in acute attacks. These attacks of neuroinflammation can lead to pathologies, including aquaporin-4 loss, astrocytic activation, injury and loss, glutamate excitotoxicity, microglial activation, neuroinflammation, demyelination, and neuronal injury, via both complement-dependent and complement-independent pathophysiological mechanisms. With the increased understanding of these mechanisms underlying this serious autoimmune astrocytopathy, effective treatments for both active attacks and long-term immunosuppression to prevent relapses in NMOSD are increasingly available based on the evidence from retrospective observational data and prospective clinical trials. Knowledge on the indications and potential side effects of these medications are essential for a clear evaluation of the potential benefits and risks to NMOSD patients in a personalized manner. Special issues such as pregnancy and the coexistence of other autoimmune diseases require additional concern and meticulous care. Future directions include the identification of clinically useful biomarkers for the prediction of relapse and monitoring of the therapeutic response, as well as the development of effective medications with minimal side effects, especially opportunistic infections complicated by long-term immunosuppression.


Assuntos
Neuromielite Óptica/terapia , Aquaporina 4/imunologia , Autoanticorpos/fisiologia , Biomarcadores/análise , Biomarcadores/sangue , Humanos , Imunossupressão/métodos , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/etiologia , Neuromielite Óptica/patologia
6.
AIDS Res Ther ; 18(1): 55, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446039

RESUMO

BACKGROUND: For over a decade, antiretroviral therapy (ART) in resource-limited countries was only recommended for patients with advanced HIV disease. We investigated this group of patients in order to determine any relationship between degree of immunosuppression during treatment initiation and the subsequent levels of inflammatory biomarkers, reservoir size and plasma marker of fungal translocation after achieving long-term virological control. METHODS: We analyzed 115 virally suppressed (female 83.5%) and 40 untreated (female 70%) subjects from Dar es Salaam, Tanzania. The size of HIV latent reservoir (proviral DNA copy) was determined using quantitative PCR. Inflammatory biomarkers; IL-6, IL-10, and soluble CD14 (sCD14), were measured using multiplex cytometric beads array. Antibody titers for Cytomegalovirus (CMV) and Epstein Barr virus (EBV), plasma level of 1-3-beta-D-Glucan (BDG) was measured using ELISA. High-sensitivity C-reactive protein (hsCRP) was measured using nephelometric method. RESULTS: The median age was 36 (IQR 32-44) and 47 (IQR 43-54) years in untreated and virally suppressed patients respectively. Median duration of treatment for virally suppressed patients was 9 years (IQR 7-12) and median baseline CD4 count was 147 cells/mm3 (IQR 65-217). Virally suppressed patients were associated with significantly lower plasma levels of IL-10, sCD14 and BDG (P < 0.05) when compared to untreated patients. However, plasma level of IL-6 was similar between the groups. Baseline advanced level of immunosuppression (CD4 < 100cells/cm3) was associated with significantly higher plasma level of IL-6 (P = 0.02), hsCRP (P = 0.036) and BDG (P = 0.0107). This relationship was not seen in plasma levels of other tested markers. Degree of baseline immunosuppression was not associated with the subsequent proviral DNA copy. In addition, plasma levels of inflammatory marker were not associated with sex, CMV or EBV antibody titers, treatment duration or regimen. CONCLUSIONS: Our data suggest that advanced immunosuppression at ART initiation is associated with severity of inflammation and elevated fungal translocation marker despite long term virological control. Further studies are needed to evaluate the potential increased burden of non-AIDS comorbidities that are linked to elevated inflammatory and fungal translocation markers as a result of the policy of HIV treatment at CD4 count < 200 cells/cm3 implemented for over a decade in Tanzania.


Assuntos
Infecções por Vírus Epstein-Barr , Infecções por HIV , Adulto , Biomarcadores , Feminino , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 4 , Humanos , Imunossupressão , Inflamação , Tanzânia
7.
J Transl Med ; 19(1): 338, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372858

RESUMO

BACKGROUND: Fine tuned balance of reactive oxygen species (ROS) is essential for tumor cells and tumor cells use immune checkpoints to evade attack form immunity system. However, it's unclear whether there is any crosstalk between these two pathways. CYB561D2, an antioxidant protein, is part of 5-gene prognosis signature in gliomas and its involvement in gliomas is unknown. Here, we aim to provide a detailed characterization of CYB561D2 in gliomas. METHODS: CYB561D2 expression was measured in clinical samples of gilomas and normal tissues. The effects of CYB561D2 on immunity related genes and tumor behaviors were investigated in glioma cell lines with various in vitro and in vivo assays. RESULTS: CYB561D2 expression was enhanced in gliomas compared to control tissues. CYB561D2 up-regulation was associated with high grading of gliomas and short survival in patients. CYB561D2 expression was induced by H2O2 in glioma cell lines. CYB561D2 and its functional product ascorbate activated STAT3 dose-dependently. CYB561D2 over-expression increased PD-L1, CCL2 and TDO2 expression, and induced immunosuppression in co-cultured T cells. In in vitro assays, CYB561D2 knock-down suppressed cell growth, colony formation, migration and promoted apoptosis. In contrast, CYB561D2 over-expression reduced survival rate in intracranial glioma model and this effect could be blocked by dominant negative-STAT3. The CYB561D2 up-regulation and the positive association of CYB561D2 with PD-L1, CCL2 and TDO2 expression were cross-validated in open-access datasets. CONCLUSIONS: CYB561D2 up-regulation induces immunosuppression and aggression via activating STAT3 in gliomas and CYB561D2 mediates ROS-tumor immunity crosstalk.


Assuntos
Neoplasias Encefálicas , Glioma , Agressão , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Humanos , Peróxido de Hidrogênio , Imunossupressão , Fator de Transcrição STAT3/metabolismo , Regulação para Cima/genética
8.
Int J Mol Sci ; 22(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361061

RESUMO

Sepsis is a sustained systemic inflammatory condition involving multiple organ failures caused by dysregulated immune response to infections. Sepsis induces substantial changes in energy demands at the cellular level leading to metabolic reprogramming in immune cells and stromal cells. Although sepsis-associated organ dysfunction and mortality have been partly attributed to the initial acute hyperinflammation and immunosuppression precipitated by a dysfunction in innate and adaptive immune responses, the late mortality due to metabolic dysfunction and immune paralysis currently represent the major problem in clinics. It is becoming increasingly recognized that intertissue and/or intercellular metabolic crosstalk via endocrine factors modulates maintenance of homeostasis, and pathological events in sepsis and other inflammatory diseases. Exosomes have emerged as a novel means of intercellular communication in the regulation of cellular metabolism, owing to their capacity to transfer bioactive payloads such as proteins, lipids, and nucleic acids to their target cells. Recent evidence demonstrates transfer of intact metabolic intermediates from cancer-associated fibroblasts via exosomes to modify metabolic signaling in recipient cells and promote cancer progression. Here, we review the metabolic regulation of endothelial cells and immune cells in sepsis and highlight the role of exosomes as mediators of cellular metabolic signaling in sepsis.


Assuntos
Células Endoteliais/patologia , Exossomos/patologia , Imunossupressão , Inflamação/patologia , Doenças Metabólicas/patologia , Sepse/fisiopatologia , Animais , Humanos , Inflamação/imunologia , Doenças Metabólicas/etiologia
9.
J Transl Med ; 19(1): 325, 2021 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-34332586

RESUMO

BACKGROUND: General role of cancer-associated fibroblast (CAF) and its infiltration characteristics in gastric cancer remains to be unknown. METHODS: We estimate CAF infiltration in bulk tumor tissue with RNA-seq data and analyzed its relationship with gastric cancer subtype, survival and immune microenvironment. RESULTS: We revealed CAF intend to have higher infiltration in diffuse, genomically stable, and advanced gastric cancer. CAF is associated with immunosuppressive microenvironment. Wide transcriptomics alterations occur in high CAF infiltrated gastric cancer, PI3K/AKT, TGFB and Hedgehog pathway are remarkable in this procedure. We utilized receptor tyrosine kinases and TGFB pathway ligands to construct risk score system that can predict survival. CONCLUSION: Thus, CAF is associated with aggressive phenotype of gastric cancer and risk score based on RTK and TGFB pathway ligands expression is a promising tool for assessment of gastric cancer survival.


Assuntos
Fibroblastos Associados a Câncer , Neoplasias Gástricas , Proteínas Hedgehog , Humanos , Imunossupressão , Fosfatidilinositol 3-Quinases , Neoplasias Gástricas/genética , Microambiente Tumoral
11.
Reumatol Clin (Engl Ed) ; 17(7): 408-419, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34301385

RESUMO

BACKGROUND: It is not clear whether patients with some degree of immunosuppression have worse outcomes in SARS-CoV-2 infection, compared to healthy people. OBJECTIVE: To carry out a narrative review of the information available on infection by SARS-CoV-2 in immunosuppressed patients, especially patients with cancer, transplanted, neurological diseases, primary and secondary immunodeficiencies. RESULTS: Patients with cancer and recent cancer treatment (chemotherapy or surgery) and SARS-CoV-2 infection have a higher risk of worse outcomes. In transplant patients (renal, cardiac and hepatic), with neurological pathologies (multiple sclerosis (MS), neuromyelitis optica (NMODS), myasthenia gravis (MG)), primary immunodeficiencies and infection with human immunodeficiency virus (HIV) in association with immunosuppressants, studies have shown no tendency for worse outcomes. CONCLUSION: Given the little evidence we have so far, the behaviour of SARS-CoV-2 infection in immunosuppressed patients is unclear, but current studies have not shown worse outcomes, except for patients with cancer.


Assuntos
COVID-19/imunologia , Hospedeiro Imunocomprometido , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Saúde Global , Humanos , Imunossupressão/efeitos adversos , Imunossupressores/efeitos adversos , Prognóstico , Índice de Gravidade de Doença
12.
Front Immunol ; 12: 598943, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211455

RESUMO

Neutrophils play an important role in the outcome of leishmaniasis, contributing either to exacerbating or controlling the progression of infection, a dual effect whose underlying mechanisms are not clear. We recently reported that CD4+ and CD8+ T cells, and dendritic cells of Leishmania amazonensis-infected mice present high expression of PD-1 and PD-L1, respectively. Given that the PD-1/PD-L1 interaction may promote cellular dysfunction, and that neutrophils could interact with T cells during infection, we investigated here the levels of PD-L1 in neutrophils exposed to Leishmania parasites. We found that both, promastigotes and amastigotes of L. amazonensis induced the expression of PD-L1 in the human and murine neutrophils that internalized these parasites in vitro. PD-L1-expressing neutrophils were also observed in the ear lesions and the draining lymph nodes of L. amazonensis-infected mice, assessed through cell cytometry and intravital microscopy. Moreover, expression of PD-L1 progressively increased in neutrophils from ear lesions as the disease evolved to the chronic phase. Co-culture of infected neutrophils with in vitro activated CD8+ T cells inhibits IFN-γ production by a mechanism dependent on PD-1 and PD-L1. Importantly, we demonstrated that in vitro infection of human neutrophils by L braziliensis induced PD-L1+ expression and also PD-L1+ neutrophils were detected in the lesions of patients with cutaneous leishmaniasis. Taken together, these findings suggest that the Leishmania parasite increases the expression of PD-L1 in neutrophils with suppressor capacity, which could favor the parasite survival through impairing the immune response.


Assuntos
Antígeno B7-H1/metabolismo , Leishmania braziliensis/fisiologia , Leishmaniose/imunologia , Neutrófilos/imunologia , Linfócitos T/imunologia , Animais , Antígeno B7-H1/genética , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Imunossupressão , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptor de Morte Celular Programada 1/metabolismo
13.
PLoS Pathog ; 17(7): e1009753, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34260666

RESUMO

To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results suggest that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings suggest biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.


Assuntos
COVID-19/imunologia , Modelos Imunológicos , SARS-CoV-2 , Biomarcadores/metabolismo , Linfócitos T CD8-Positivos/imunologia , COVID-19/virologia , Estudos de Coortes , Biologia Computacional , Simulação por Computador , Suscetibilidade a Doenças/imunologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunidade Inata , Imunossupressão , Interferons/metabolismo , Interleucina-6/metabolismo , Macrófagos/imunologia , Pandemias , SARS-CoV-2/imunologia , Índice de Gravidade de Doença , Interface Usuário-Computador
14.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198513

RESUMO

BACKGROUND: Pulmonary disease caused by Mycobacterium abscessus (M. abscessus) spreads around the world, and this disease is extremely difficult to treat due to intrinsic and acquired resistance of the pathogen to many approved antibiotics. M. abscessus is regarded as one of the most drug-resistant mycobacteria, with very limited therapeutic options. METHODS: Whole-cell growth inhibition assays was performed to screen and identify novel inhibitors. The IC50 of the target compounds were tested against THP-1 cells was determined to calculate the selectivity index, and then time-kill kinetics assay was performed against M. abscessus. Subsequently, the synergy of oritavancin with other antibiotics was evaluated by using checkerboard method. Finally, in vivo efficacy was determined in an immunosuppressive murine model simulating M. abscessus infection. RESULTS: We have identified oritavancin as a potential agent against M. abscessus. Oritavancin exhibited time-concentration dependent bactericidal activity against M. abscessus and it also displayed synergy with clarithromycin, tigecycline, cefoxitin, moxifloxacin, and meropenem in vitro. Additionally, oritavancin had bactericidal effect on intracellular M. abscessus. Oritavancin significantly reduced bacterial load in lung when it was used alone or in combination with cefoxitin and meropenem. CONCLUSIONS: Our in vitro and in vivo assay results indicated that oritavancin may be a viable treatment option against M. abscessus infection.


Assuntos
Antibacterianos/uso terapêutico , Lipoglicopeptídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/fisiologia , Animais , Antibacterianos/farmacologia , Modelos Animais de Doenças , Sinergismo Farmacológico , Humanos , Imunossupressão , Espaço Intracelular/microbiologia , Lipoglicopeptídeos/farmacologia , Camundongos , Testes de Sensibilidade Microbiana , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Células THP-1
15.
Int J Mol Sci ; 22(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208157

RESUMO

Advanced imaging techniques for diagnosis have increased awareness on the benefits of brain screening, facilitated effective control of extracranial disease, and prolonged life expectancy of metastatic renal cell carcinoma (mRCC) patients. Brain metastasis (BM) in patients with mRCC (RCC-BM) is associated with grave prognoses, a high degree of morbidity, dedicated assessment, and unresponsiveness to conventional systemic therapeutics. The therapeutic landscape of RCC-BM is rapidly changing; however, survival outcomes remain poor despite standard surgery and radiation, highlighting the unmet medical needs and the requisite for advancement in systemic therapies. Immune checkpoint inhibitors (ICIs) are one of the most promising strategies to treat RCC-BM. Understanding the role of brain-specific tumor immune microenvironment (TIME) is important for developing rationale-driven ICI-based combination strategies that circumvent tumor intrinsic and extrinsic factors and complex positive feedback loops associated with resistance to ICIs in RCC-BM via combination with ICIs involving other immunological pathways, anti-antiangiogenic multiple tyrosine kinase inhibitors, and radiotherapy; therefore, novel combination approaches are being developed for synergistic potential against RCC-BM; however, further prospective investigations with longer follow-up periods are required to improve the efficacy and safety of combination treatments and to elucidate dynamic predictive biomarkers depending on the interactions in the brain TIME.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/terapia , Carcinoma de Células Renais/patologia , Imunoterapia , Neoplasias Renais/patologia , Humanos , Imunossupressão , Microambiente Tumoral
16.
Dtsch Med Wochenschr ; 146(13-14): 891-893, 2021 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-34256402

RESUMO

During COVID 19 pandemic patients typically present with respiratory symptoms. However, in a significant number of patients the gastrointestinal tract is also involved in the disease. Up to 20 % of patients suffering from gastrointestinal symptoms. New insights in pathophysiological aspects might open new therapeutic concepts. This up-date includes current data regarding epidemiology of gastrointestinal symptoms in COVID 19, its role for prognosis and specific risks in relation to immunosuppressive therapies and underlying diseases.


Assuntos
COVID-19/complicações , Gastroenteropatias/etiologia , Hepatopatias/virologia , Pancreatopatias/virologia , SARS-CoV-2/fisiologia , Gastroenteropatias/epidemiologia , Gastroenteropatias/terapia , Humanos , Imunossupressão/efeitos adversos , Prevalência , Prognóstico , Fatores de Risco , SARS-CoV-2/patogenicidade
17.
Oncoimmunology ; 10(1): 1940673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34290904

RESUMO

Introduction: Despite the advent of immunotherapy as a promising therapeutic, glioblastoma (GBM) remains resistant to using checkpoint blockade due to its highly immunosuppressive tumor milieu. Moreover, current anti-PD-1 treatment requires multiple infusions with adverse systemic effects. Therefore, we used a PCL:PEG:PCL polymer gel loaded with anti-PD-1 and implanted at the site of lymph nodes in an attempt to maximize targeting of inactivated T cells as well as mitigate unnecessary systemic exposure. Methods: Mice orthotopically implanted with GL261 glioma cells were injected with hydrogels loaded with anti-PD-1 in one of the following locations: cervical lymph nodes, inguinal lymph nodes, and the tumor site. Mice treated systemically with anti-PD-1 were used as comparative controls. Kaplan-Meier curves were generated for all arms, with ex vivo flow cytometric staining for L/D, CD45, CD3, CD4, CD8, TNF-α and IFN-y and co-culture ELISpots were done for immune cell activation assays. Results: Mice implanted with PCL:PEG:PCL hydrogels carrying anti-PD-1 at the site of their lymph nodes showed significantly improved survival outcomes compared to mice systemically treated with anti-PD-1 (P = .0185). Flow cytometric analysis of brain tissue and co-culture of lymph node T cells from mice implanted with gels demonstrated increased levels of IFN-y and TNF-α compared to mice treated with systemic anti-PD-1, indicating greater reversal of immunosuppression compared to systemic treatment. Conclusions: Our data demonstrate proof of principle for using localized therapy that targets lymph nodes for GBM. We propose an alternative treatment paradigm for developing new sustained local treatments with immunotherapy that are able to eliminate the need for multiple systemic infusions and their off-target effects.


Assuntos
Glioblastoma , Glioma , Animais , Glioblastoma/tratamento farmacológico , Imunossupressão , Imunoterapia , Linfonodos , Camundongos
18.
Washington, D.C.; OPS; 2021-07-27. (OPS/CDE/VT/21-0008).
Não convencional em Espanhol | PAHO-IRIS | ID: phr-54561

RESUMO

Según las estimaciones, en las Américas hay entre 6 y 8 millones de personas con infección por T. cruzi, con aproximadamente 30 000 casos nuevos por año por transmisión vectorial, y 8000 casos nuevos anuales por transmisión congénita. Es decir, cerca de 65 millones de personas viven en la Región con el riesgo de contraer la infección. Además, durante cualquiera de las fases de esta parasitosis, las personas con la infección pueden sufrir algún grado de inmunosupresión, bien sea por una infección, una neoplasia o por un tratamiento farmacológico. En este decálogo se exponen los conceptos más importantes para tener en cuenta frente a la coexistencia de inmunosupresión y la infección por el T. cruzi.


Assuntos
Trypanosoma cruzi , Doença de Chagas , Doenças Transmitidas por Vetores , Anormalidades Congênitas , Parasitos , Imunossupressão , Doenças Parasitárias , Doenças Transmissíveis
19.
J Cardiothorac Surg ; 16(1): 159, 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34078389

RESUMO

BACKGROUND: In systolic chronic heart failure, a heterogeneous blood volume (BV) regulation can be found with plasma volume expansion in many cases, possibly leading to pseudoanemia. Little is known about the volume status after heart transplantation (HTX). So far, anemia of HTX recipients was solely investigated using hemoglobin-concentration that may be misleading in a clinical context. The objective of the study was whether a difference in plasma volume and red cell volume can be observed in clinically stable heart transplant recipients compared to matched control subjects. Secondary, the aim was to describe anemia in the long-term after HTX based on quantitative data. METHODS: Blood volume and its constituents red cell volume and plasma volume were quantified using an abbreviated carbon monoxide rebreathing method (aCORM) with focus on its primary measure total hemoglobin mass (Hbmass) and coincidental anemia in 36 (7 women) heart transplant recipients. For comparison, a matched control group of 46 (5 women) healthy subjects was selected. RESULTS: Neither Hbmass nor blood volumes were significantly different in HTX patients compared to matched healthy control group subjects. The prevalence of anemia 6.3 ± 4.3 years after transplantation was 19%. Hbmass and red cell volume were significantly lower in anemic HTX patients compared to non-anemic patients while plasma volume was not expanded. Various immunosuppressant regimens did not have an effect on Hbmass, plasma volume or red cell volume. CONCLUSIONS: There was no difference in blood volumes and Hbmass between HTX patients and control subjects. The pathophysiologic blood volume regulation in chronic heart failure does not seem to be longer active in long-term HTX recipients. However, in the long-term after HTX, anemia occurs in a considerable number of patients as true anemia without a clear association with immunosuppression. TRIAL REGISTRATION: German registry for clinical studies, DRKS00006078. Registered 09 May 2014, https://www.drks.de/drks_web/navigate.do?navigationId=trial . HTML&TRIAL_ID=DRKS00006078.


Assuntos
Anemia/sangue , Volume de Eritrócitos , Transplante de Coração , Hemoglobinas/metabolismo , Volume Plasmático , Adulto , Idoso , Estudos de Casos e Controles , Estudos Transversais , Feminino , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/cirurgia , Humanos , Imunossupressão , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
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