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  1 / 152683 MEDLINE  
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[PMID]:29460640
[Au] Autor:Sullivan A; Watkinson J; Waddington J; Park BK; Naisbitt DJ
[Ad] Endereço:a MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology , The University of Liverpool , Liverpool , England.
[Ti] Título:Implications of HLA-allele associations for the study of type IV drug hypersensitivity reactions.
[So] Source:Expert Opin Drug Metab Toxicol;14(3):261-274, 2018 Mar.
[Is] ISSN:1744-7607
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Type IV drug hypersensitivity remains an important clinical problem and an obstacle to the development of new drugs. Several forms of drug hypersensitivity are associated with expression of specific HLA alleles. Furthermore, drug-specific T-lymphocytes have been isolated from patients with reactions. Despite this, controversy remains as to how drugs interact with immune receptors to stimulate a T-cell response. Areas covered: This article reviews the pathways of T-cell activation by drugs and how the ever increasing number of associations between expression of HLA alleles and susceptibility to hypersensitivity is impacting on our research effort to understanding this form of iatrogenic disease. Expert opinion: For a drug to activate a T-cell, a complex is formed between HLA molecules, an HLA binding peptide, the drug and the T-cell receptor. T-cell responses can involve drugs and stable or reactive metabolites bound covalently or non-covalently to any component of this complex. Recent research has linked the HLA associations to the disease through the characterization of drug-specific T-cell responses restricted to specific alleles. However, there is now a need to identify the additional genetic or environment factors that determine susceptibility and use our increased knowledge to develop predictive immunogenicity tests that offer benefit to Pharma developing new drugs.
[Mh] Termos MeSH primário: Hipersensibilidade a Drogas/imunologia
Antígenos HLA/imunologia
Hipersensibilidade Tardia/induzido quimicamente
[Mh] Termos MeSH secundário: Alelos
Hipersensibilidade a Drogas/genética
Predisposição Genética para Doença
Seres Humanos
Hipersensibilidade Tardia/genética
Hipersensibilidade Tardia/imunologia
Ativação Linfocitária/efeitos dos fármacos
Ativação Linfocitária/imunologia
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (HLA Antigens)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180221
[St] Status:MEDLINE
[do] DOI:10.1080/17425255.2018.1441285


  2 / 152683 MEDLINE  
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[PMID]:29446280
[Au] Autor:Stepanenko LA; Savchenkov MF; Ilina SV; Anganova EV; Savilov ED
[Ti] Título:[An assessment of the immune status of the children population as a marker of technogenic pollution of the environment].
[So] Source:Gig Sanit;95(12):1129-33, 2016.
[Is] ISSN:0016-9900
[Cp] País de publicação:Russia (Federation)
[La] Idioma:rus
[Ab] Resumo:This article describes results of the immunological study of school-aged children residing in cities with different levels of the technogenic air pollution. Children from cities with the highest level of the technogenic pollution had a high number of immature neutrophils (band cells) and eosinophils. The children living in these ecologically unfavorable areas have presented a reduction of T-cell antigen receptor CD3, CD4, CD8, CD20, CD16, CD95. This indicates to that both T-cell and B-cell immunity is suppressed. The decline of the phagocytic function in neutrophils indicates to the suppression of the nonspecific host defense mechanisms also.
[Mh] Termos MeSH primário: Poluentes Atmosféricos
Linfócitos B/imunologia
Exposição Ambiental
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Poluentes Atmosféricos/efeitos adversos
Poluentes Atmosféricos/análise
Criança
Exposição Ambiental/efeitos adversos
Exposição Ambiental/análise
Exposição Ambiental/prevenção & controle
Feminino
Seres Humanos
Imunocompetência/efeitos dos fármacos
Masculino
Monitorização Imunológica/métodos
Monitorização Imunológica/estatística & dados numéricos
População
Receptores de Antígenos de Linfócitos T/análise
Serviços de Saúde Escolar/organização & administração
Serviços de Saúde Escolar/estatística & dados numéricos
Sibéria/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Air Pollutants); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180216
[St] Status:MEDLINE


  3 / 152683 MEDLINE  
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[PMID]:29412476
[Au] Autor:Bakela K; Dimakopoulou M; Batsou P; Manidakis N; Athanassakis I
[Ad] Endereço:Laboratory of Immunology, Department of Biology, University of Crete, Heraklion, Crete, Greece.
[Ti] Título:Soluble MHC class II-driven therapy for a systemic lupus erythematosus murine experimental in vitro and in vivo model.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Taking into consideration the multiparametric nature of systemic lupus erythematosus (SLE), the severity and variability of symptoms and the lack of effective therapeutic approaches, this study took advantage of the recently described role of soluble major histocompatibility complex class II (sMHCII) molecules in maintaining tolerance to the organism and attempted to apply sMHCII proteins as a treatment to murine SLE experimental models in vitro as well as in vivo. After breaking tolerance to DNA in vitro, which was accompanied by development of specific anti-dsDNA antibodies, syngeneic or allogeneic sMHCII molecules, purified from healthy mouse serum, could significantly reduce the specific antibody levels and drive the system towards immunosuppression, as assessed by specific marker analysis on T cells and cytokine production by flow cytometry and ELISA, respectively. The in vivo experimental model consisted of pristane-induced SLE symptoms to BALB/c mice, which developed maximal levels of anti-dsDNA 2 months after pristane inoculation. Syngeneic or allogeneic sMHCII administration could alleviate pristane-induced symptoms, significantly decrease specific anti-dsDNA antibody production and develop immunosuppression to the host, as manifested by increase of CD4 + CTLA-4 +  and CD4 + CD25 +  cell populations in the spleen. Thus, the results presented in this study introduced the ability of sMHCII proteins to suppress specific autoantigen response, opening new areas of research and offering novel therapeutic approaches to SLE with expanding features to other autoimmune diseases.
[Mh] Termos MeSH primário: Anticorpos Antinucleares/imunologia
Autoantígenos/imunologia
Antígenos de Histocompatibilidade Classe II/imunologia
Tolerância Imunológica/imunologia
Imunoterapia/métodos
Lúpus Eritematoso Sistêmico/imunologia
Lúpus Eritematoso Sistêmico/terapia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos CD4/metabolismo
Antígeno CTLA-4/metabolismo
Células Cultivadas
DNA/imunologia
Modelos Animais de Doenças
Imunossupressão
Subunidade alfa de Receptor de Interleucina-2/metabolismo
Lúpus Eritematoso Sistêmico/induzido quimicamente
Camundongos
Camundongos Endogâmicos BALB C
Baço/citologia
Baço/imunologia
Terpenos/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Antinuclear); 0 (Autoantigens); 0 (CD4 Antigens); 0 (CTLA-4 Antigen); 0 (Histocompatibility Antigens Class II); 0 (Il2ra protein, mouse); 0 (Interleukin-2 Receptor alpha Subunit); 0 (Terpenes); 26HZV48DT1 (pristane); 9007-49-2 (DNA)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12644


  4 / 152683 MEDLINE  
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[PMID]:29381830
[Au] Autor:Sioud M
[Ad] Endereço:Department of Cancer Immunology, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
[Ti] Título:T-cell cross-reactivity may explain the large variation in how cancer patients respond to checkpoint inhibitors.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The therapeutic use of the immune system to specifically attack tumours has been a long-standing vision among tumour immunologists. Recently, the use of checkpoint inhibitors to turn-off immunosuppressive signals has proven to be effective in enhancing T-cell reactivity against patient-specific neoantigens, resulting from somatic mutations. Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre-existing microbial cross-reactive T cells in rapid and durable tumour regression seen in some patients. This notion of T-cell cross-reactivity is further supported by the findings that intestinal bacteria can influence checkpoint-blockade therapy. Moreover, early data indicate the presence of such T cells in long-term survival breast cancer patients. This review highlights the main challenges for cancer immunotherapy and discusses the potential contribution of T-cell cross-reactivity in cancer immunotherapy and whether it can be used as a biomarker to predict the responsiveness to checkpoint inhibitors.
[Mh] Termos MeSH primário: Reações Cruzadas/imunologia
Imunoterapia/métodos
Neoplasias/imunologia
Neoplasias/terapia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Antígenos de Bactérias/imunologia
Antígenos de Neoplasias/imunologia
Antígenos Virais/imunologia
Biomarcadores Tumorais/imunologia
Antígeno CTLA-4/antagonistas & inibidores
Células Dendríticas/imunologia
Epitopos de Linfócito T/imunologia
Seres Humanos
Ativação Linfocitária/imunologia
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Receptores Imunológicos/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Antigens, Neoplasm); 0 (Antigens, Viral); 0 (Biomarkers, Tumor); 0 (CTLA-4 Antigen); 0 (Epitopes, T-Lymphocyte); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 0 (Receptors, Immunologic); 0 (TIGIT protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12643


  5 / 152683 MEDLINE  
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[PMID]:29377916
[Au] Autor:Tutykhina I; Esmagambetov I; Bagaev A; Pichugin A; Lysenko A; Shcherbinin D; Sedova E; Logunov D; Shmarov M; Ataullakhanov R; Naroditsky B; Gintsburg A
[Ad] Endereço:Federal Research Centre of Epidemiology and Microbiology named after Honorary Academician N. F. Gamaleya, Ministry of Health, Moscow, Russia.
[Ti] Título:Vaccination potential of B and T epitope-enriched NP and M2 against Influenza A viruses from different clades and hosts.
[So] Source:PLoS One;13(1):e0191574, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:To avoid outbreaks of influenza virus epidemics and pandemics among human populations, modern medicine requires the development of new universal vaccines that are able to provide protection from a wide range of influenza A virus strains. In the course of development of a universal vaccine, it is necessary to consider that immunity must be generated even against viruses from different hosts because new human epidemic virus strains have their origins in viruses of birds and other animals. We have enriched conserved viral proteins-nucleoprotein (NP) and matrix protein 2 (M2)-by B and T-cell epitopes not only human origin but also swine and avian origin. For this purpose, we analyzed M2 and NP sequences with respect to changes in the sequences of known T and B-cell epitopes and chose conserved and evolutionarily significant epitopes. Eventually, we found consensus sequences of M2 and NP that have the maximum quantity of epitopes that are 100% coincident with them. Consensus epitope-enriched amino acid sequences of M2 and NP proteins were included in a recombinant adenoviral vector. Immunization with Ad5-tet-M2NP induced strong CD8 and CD4 T cells responses, specific to each of the encoded antigens, i.e. M2 and NP. Eight months after immunization with Ad5-tet-M2NP, high numbers of M2- and NP-responding "effector memory" CD44posCD62neg T cells were found in the mouse spleens, which revealed a long-term T cell immune memory conferred by the immunization. In all, the challenge experiments showed an extraordinarily wide-ranging efficacy of protection by the Ad5-tet-M2NP vaccine, covering 5 different heterosubtypes of influenza A virus (2 human, 2 avian and 1 swine).
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Epitopos/imunologia
Vírus da Influenza A/imunologia
Nucleoproteínas/imunologia
Linfócitos T/imunologia
Vacinação
Proteínas da Matriz Viral/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Antivirais/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Viral); 0 (Epitopes); 0 (Nucleoproteins); 0 (Viral Matrix Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191574


  6 / 152683 MEDLINE  
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[PMID]:29362889
[Au] Autor:Gaudio F; Tamma R; Ingravallo G; Perrone T; Laddaga FE; De Candia M; Maiorano E; Ribatti D; Specchia G
[Ad] Endereço:Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology Section, University of Bari, Bari, Italy. fragaudio@alice.it.
[Ti] Título:Computer-driven quantitative image analysis in the assessment of tumor cell and T cell features in diffuse large B cell lymphomas.
[So] Source:Ann Hematol;97(4):663-668, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Diffuse large B cell lymphoma (DLBCL) is recognized as the most common non-Hodgkin lymphoma subtype. Advanced high-resolution digital scans of pathology slides have enabled the development of computer-based image analysis algorithms that may assist pathologists in quantifying immunohistochemical stains. In this retrospective study, we reviewed data from 29 patients affected by DLBCL. In order to evaluate the number of tumor cells and microenvironment T cells, we performed an analysis of CD20, Ki67, and CD3 counts, assessed with the Positive Pixel Count algorithm embedded in the Aperio ImageScope software. A lower tumor cell count was observed in patients with a non-germinal center immunophenotype, high LDH, splenomegaly and an IPI ≥ 3. A lower number of CD3 was observed in patients with bulky disease, an IPI ≥ 3 and disease stage 3-4. Overall, these data confirm that quantitative analysis of the tumor cells and of the tumor microenvironment by means of computer-driven quantitative image analysis may add new information in DLBCL diagnosis.
[Mh] Termos MeSH primário: Linfócitos B/patologia
Interpretação de Imagem Assistida por Computador
Linfonodos/diagnóstico por imagem
Linfoma Difuso de Grandes Células B/diagnóstico por imagem
Linfócitos T/patologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Algoritmos
Antígenos CD20/metabolismo
Linfócitos B/imunologia
Linfócitos B/metabolismo
Complexo CD3/metabolismo
Feminino
Centro Germinativo/imunologia
Centro Germinativo/metabolismo
Centro Germinativo/patologia
Seres Humanos
Imuno-Histoquímica
Antígeno Ki-67/metabolismo
Linfonodos/imunologia
Linfonodos/metabolismo
Linfonodos/patologia
Linfoma Difuso de Grandes Células B/imunologia
Linfoma Difuso de Grandes Células B/metabolismo
Linfoma Difuso de Grandes Células B/patologia
Masculino
Meia-Idade
Estadiamento de Neoplasias
Prognóstico
Estudos Retrospectivos
Linfócitos T/imunologia
Linfócitos T/metabolismo
Microambiente Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (CD3 Complex); 0 (Ki-67 Antigen)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180125
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3212-6


  7 / 152683 MEDLINE  
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[PMID]:28467721
[Au] Autor:Sareila O; Hagert C; Kelkka T; Linja M; Xu B; Kihlberg J; Holmdahl R
[Ad] Endereço:1 Medicity Research Laboratory, University of Turku , Turku, Finland .
[Ti] Título:Reactive Oxygen Species Regulate Both Priming and Established Arthritis, but with Different Mechanisms.
[So] Source:Antioxid Redox Signal;27(18):1473-1490, 2017 Dec 20.
[Is] ISSN:1557-7716
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIMS: Neutrophil cytosolic factor 1 (NCF1) is a key regulatory component of the phagocytic NOX2 complex, which produces reactive oxygen species (ROS). Polymorphism of the Ncf1 gene is associated with increased arthritis severity. In this study, we generated targeted Ncf1 knock-in mice with inducible Ncf1 expression and determined the critical time window during which the NOX2-derived ROS protect the mice from arthritis. RESULTS: Targeted Ncf1 knock-in mice lacked NOX2-derived ROS, and in vivo allelic conversion of Ncf1 by the CreER recombinase led to full protein expression and ROS production within 10 days. Mice in which Ncf1 had been activated before immunization with type II collagen (CII) developed only mild clinical symptoms of collagen-induced arthritis (CIA), whereas the ROS-deficient littermates had severe arthritis. The functional Ncf1 restricted the expansion of IL-17A-producing T cells specific for the immunodominant CII peptide. When the Ncf1 gene was activated after the priming phase, Ncf1-dependent protection from autoimmune arthritis was still observed, together with a reduced number of splenic monocytes but it was not associated with alterations in peptide-specific T cell response. The Ncf1-deficient mice expressed pronounced interferon signature, which could be normalized by conditional expression of Ncf1 and was also present in the Ncf1-mutated mouse during arthritis. Innovation and Conclusion: Ncf1 deficiency has been known to predispose to autoimmunity in both humans and rodents. Our in vivo results point to a regulatory role of NOX2-derived ROS not only during priming but also during the effector phase of CIA, most likely via different mechanisms. Antioxid. Redox Signal. 27, 1473-1490.
[Mh] Termos MeSH primário: Artrite Experimental/metabolismo
NADPH Oxidases/genética
NADPH Oxidases/metabolismo
Espécies Reativas de Oxigênio/metabolismo
[Mh] Termos MeSH secundário: Animais
Artrite Experimental/induzido quimicamente
Artrite Experimental/genética
Colágeno Tipo II/efeitos adversos
Modelos Animais de Doenças
Técnicas de Introdução de Genes
Seres Humanos
Interleucina-17/metabolismo
Camundongos
Linfócitos T/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Collagen Type II); 0 (Interleukin-17); 0 (Reactive Oxygen Species); EC 1.6.3.- (NADPH Oxidases); EC 1.6.3.1 (neutrophil cytosolic factor 1)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1089/ars.2016.6981


  8 / 152683 MEDLINE  
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[PMID]:28467275
[Au] Autor:Dos Santos PF; Mansur DS
[Ad] Endereço:Departament of Microbiology, Immunology and Parasitology, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina , Santa Catarina, Brazil .
[Ti] Título:Beyond ISGlylation: Functions of Free Intracellular and Extracellular ISG15.
[So] Source:J Interferon Cytokine Res;37(6):246-253, 2017 Jun.
[Is] ISSN:1557-7465
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:ISG15 is a ubiquitin-like type I IFN-stimulated protein of 15 kDa and is one of the most prominently expressed proteins in viral infections. ISG15 is widely known to be involved in a process called ISGylation, where it binds to over 150 targets from a variety of classes of proteins including central immune signaling pathways such as those mediated by NFκB, JNK, and IRF-3. However, ISG15 also exists in a free form that can act intra- or extracellularly. In vitro and in vivo evidences suggest that free ISG15 play different roles in several cellular processes, from cancer and defense against viral infections to activation of immune cells such as lymphocytes, monocytes, and NK cells. This review discusses the roles of free intracellular and secreted ISG15 approaching questions yet to be answered about the mechanism of action of this protein.
[Mh] Termos MeSH primário: Infecções Bacterianas/imunologia
Citocinas/imunologia
Interferon gama/imunologia
Transdução de Sinais/imunologia
Ubiquitinas/imunologia
Viroses/imunologia
[Mh] Termos MeSH secundário: Infecções Bacterianas/genética
Infecções Bacterianas/microbiologia
Citocinas/genética
Regulação da Expressão Gênica
Seres Humanos
Fator Regulador 3 de Interferon/genética
Fator Regulador 3 de Interferon/imunologia
Interferon Tipo I/genética
Interferon Tipo I/imunologia
Interferon gama/genética
Monócitos/imunologia
Monócitos/microbiologia
Monócitos/virologia
Neutrófilos/imunologia
Neutrófilos/microbiologia
Neutrófilos/virologia
Linfócitos T/imunologia
Linfócitos T/microbiologia
Linfócitos T/virologia
Ubiquitinas/genética
Viroses/genética
Viroses/virologia
eIF-2 Quinase/genética
eIF-2 Quinase/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cytokines); 0 (IRF3 protein, human); 0 (Interferon Regulatory Factor-3); 0 (Interferon Type I); 0 (Ubiquitins); 60267-61-0 (ISG15 protein, human); 82115-62-6 (Interferon-gamma); EC 2.7.11.1 (eIF-2 Kinase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170504
[St] Status:MEDLINE
[do] DOI:10.1089/jir.2016.0103


  9 / 152683 MEDLINE  
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[PMID]:29422654
[Au] Autor:Marcou Q; Mora T; Walczak AM
[Ad] Endereço:Laboratoire de Physique Théorique, CNRS, Sorbonne Université and École Normale Supérieure (PSL), 24, Rue Lhomond, 75005, Paris, France.
[Ti] Título:High-throughput immune repertoire analysis with IGoR.
[So] Source:Nat Commun;9(1):561, 2018 02 08.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:High-throughput immune repertoire sequencing is promising to lead to new statistical diagnostic tools for medicine and biology. Successful implementations of these methods require a correct characterization, analysis, and interpretation of these data sets. We present IGoR (Inference and Generation Of Repertoires)-a comprehensive tool that takes B or T cell receptor sequence reads and quantitatively characterizes the statistics of receptor generation from both cDNA and gDNA. It probabilistically annotates sequences and its modular structure can be used to investigate models of increasing biological complexity for different organisms. For B cells, IGoR returns the hypermutation statistics, which we use to reveal co-localization of hypermutations along the sequence. We demonstrate that IGoR outperforms existing tools in accuracy and estimate the sample sizes needed for reliable repertoire characterization.
[Mh] Termos MeSH primário: Linfócitos B/imunologia
Receptores de Antígenos de Linfócitos B/genética
Receptores de Antígenos de Linfócitos T/genética
Software
Linfócitos T/imunologia
Recombinação V(D)J
[Mh] Termos MeSH secundário: Linfócitos B/citologia
Sequência de Bases
Benchmarking
DNA Complementar/genética
DNA Complementar/imunologia
Expressão Gênica
Sequenciamento de Nucleotídeos em Larga Escala
Seres Humanos
Imunidade Inata
Anotação de Sequência Molecular
Receptores de Antígenos de Linfócitos B/imunologia
Receptores de Antígenos de Linfócitos T/imunologia
Linfócitos T/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (Receptors, Antigen, B-Cell); 0 (Receptors, Antigen, T-Cell)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180210
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-018-02832-w


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[PMID]:28922789
[Au] Autor:Mlecnik B; Van den Eynde M; Bindea G; Church SE; Vasaturo A; Fredriksen T; Lafontaine L; Haicheur N; Marliot F; Debetancourt D; Pairet G; Jouret-Mourin A; Gigot JF; Hubert C; Danse E; Dragean C; Carrasco J; Humblet Y; Valge-Archer V; Berger A; Pagès F; Machiels JP; Galon J
[Ad] Endereço:Laboratory of Integrative Cancer Immunology, INSERM, UMRS1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, UMRS1138, Paris, France; Sorbonne Universités, UPMC Univ Paris 06, UMRS1138, Centre de Recherche des Cordeliers, Paris, France; Inovarion, Paris, France; Department of Medic
[Ti] Título:Comprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: This study assesses how the metastatic immune landscape is impacting the response to treatment and the outcome of colorectal cancer (CRC) patients. Methods: Complete curative resection of metastases (n = 441) was performed for two patient cohorts (n = 153). Immune densities were quantified in the center and invasive margin of all metastases. Immunoscore and T and B cell (TB) score were analyzed in relation to radiological and pathological responses and patient's disease-free (DFS) and overall survival (OS) using multivariable Cox proportional hazards models. All statistical tests were two-sided. Results: The spatial distribution of immune cells within metastases was nonuniform. Patients, as well as metastases of the same patient, had variable immune infiltrates and response to therapy. A beneficial response was statistically significantly associated with increased immune densities. Among all metastases, Immunoscore (I) and TB score evaluated in the least immune-infiltrated metastases were the strongest predictors for DFS and OS (five-year follow-up, Immunoscore: I 3-4: DFS rate = 27.9%, 95% CI = 15.2 to 51.3; vs I 0-1-2: DFS rate = 12.3%, 95% CI = 4.9 to 30.6; HR = 0.45, 95% CI = 0.28 to 0.70, P = .02; I 3-4: OS rate = 64.6%, 95% CI = 46.6 to 89.6; vs I 0-1-2: OS rate = 32.5%, 95% CI = 17.2 to 61.4; HR = 0.32, 95% CI = 0.15 to 0.66, P = .001, C-index = 65.9%; five-year follow-up, TB score: TB 3-4: DFS rate = 25.7%, 95% CI = 14.2 to 46.6; vs TB 0-1-2: DFS rate = 5.0%, 95% CI = 0.8 to 32.4; HR = 0.36, 95% CI = 0.22 to 0.57, P < .001; TB 3-4: OS rate = 63.7%, 95% CI = 46.4 to 87.5; vs TB 0-1-2: OS rate: 21.4%, 95% CI = 9.2 to 49.8; HR = 0.25, 95% CI = 0.12 to 0.51, P < .001, C-index = 67.8%). High TB score and Immunoscore patients had a median survival of 70.5 months, while low patients survived only 25.1 to 38.3 months. Nonresponding patients with high-immune infiltrates had prolonged DFS (HR = 0.28, 95% CI = 0.15 to 0.52, P = .001) and OS (HR = 0.25, 95% CI = 0.1 to 0.62, P = .001). The immune parameters remained the only statistically significant prognostic factor associated with DFS and OS in multivariable analysis (P < .001), while response to treatment was not. Conclusions: Response to treatment and prolonged survival of metastatic CRC patients were statistically significantly associated with high-immune densities quantified into the least immune-infiltrated metastasis.
[Mh] Termos MeSH primário: Linfócitos B
Neoplasias Colorretais/imunologia
Neoplasias Hepáticas/imunologia
Neoplasias Pulmonares/imunologia
Linfócitos do Interstício Tumoral
Linfócitos T
[Mh] Termos MeSH secundário: Idoso
Antígenos CD20/análise
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Linfócitos B/química
Complexo CD3/análise
Linfócitos T CD8-Positivos
Quimioterapia Adjuvante
Neoplasias Colorretais/patologia
Neoplasias Colorretais/terapia
Intervalo Livre de Doença
Seguimentos
Fatores de Transcrição Forkhead/análise
Hepatectomia
Seres Humanos
Antígenos Comuns de Leucócito/análise
Neoplasias Hepáticas/secundário
Neoplasias Hepáticas/terapia
Neoplasias Pulmonares/secundário
Neoplasias Pulmonares/terapia
Contagem de Linfócitos
Metastasectomia
Meia-Idade
Metástase Neoplásica
Pneumonectomia
Período Pré-Operatório
Critérios de Avaliação de Resposta em Tumores Sólidos
Taxa de Sobrevida
Linfócitos T/química
Microambiente Tumoral/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, CD20); 0 (CD3 Complex); 0 (FOXP3 protein, human); 0 (Forkhead Transcription Factors); EC 3.1.3.48 (Leukocyte Common Antigens)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx123



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