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[PMID]:28922790
[Au] Autor:Marisa L; Svrcek M; Collura A; Becht E; Cervera P; Wanherdrick K; Buhard O; Goloudina A; Jonchère V; Selves J; Milano G; Guenot D; Cohen R; Colas C; Laurent-Puig P; Olschwang S; Lefèvre JH; Parc Y; Boige V; Lepage C; André T; Fléjou JF; Dérangère V; Ghiringhelli F; de Reynies A; Duval A
[Ad] Endereço:Programme "Cartes d'Identité des Tumeurs," Ligue Nationale Contre le Cancer, Paris, France; INSERM, UMRS 938 - Centre de Recherche Saint-Antoine, Equipe "Instabilité des Microsatellites et Cancers," Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France; Sorbonne Université, UPMC U
[Ti] Título:The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors.
[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: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided. Results: The expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004). Conclusions: ICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Biomarcadores Tumorais/imunologia
Neoplasias Colorretais/genética
Neoplasias Colorretais/imunologia
Linfócitos do Interstício Tumoral
Linfócitos T Citotóxicos
[Mh] Termos MeSH secundário: Antígenos CD/genética
Antígeno B7-H1/análise
Antígeno B7-H1/genética
Antígenos CD8/análise
Antígeno CTLA-4/genética
Colo/química
Neoplasias Colorretais/química
Neoplasias Colorretais/patologia
Feminino
Expressão Gênica
Receptor Celular 2 do Vírus da Hepatite A/genética
Seres Humanos
Proteína Coestimuladora de Linfócitos T Induzíveis/genética
Masculino
Instabilidade de Microssatélites
Meia-Idade
Estadiamento de Neoplasias
Prognóstico
Proteína 2 Ligante de Morte Celular Programada 1/genética
Receptor de Morte Celular Programada 1/genética
Estudos Retrospectivos
Taxa de Sobrevida
Células Th1
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antigens, CD); 0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD223 antigen); 0 (CD274 protein, human); 0 (CD8 Antigens); 0 (CTLA-4 Antigen); 0 (HAVCR2 protein, human); 0 (Hepatitis A Virus Cellular Receptor 2); 0 (ICOS protein, human); 0 (Inducible T-Cell Co-Stimulator Protein); 0 (PDCD1 protein, human); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Programmed Cell Death 1 Receptor)
[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/djx136


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[PMID]:28850584
[Au] Autor:Turner JS; Benet ZL; Grigorova I
[Ad] Endereço:Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
[Ti] Título:Transiently antigen primed B cells can generate multiple subsets of memory cells.
[So] Source:PLoS One;12(8):e0183877, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Memory B cells are long-lived cells that generate a more vigorous response upon recognition of antigen (Ag) and T cell help than naïve B cells and ensure maintenance of durable humoral immunity. Functionally distinct subsets of murine memory B cells have been identified based on isotype switching of BCRs and surface expression of the co-stimulatory molecule CD80 and co-inhibitory molecule PD-L2. Memory B cells in a subpopulation with low surface expression of CD80 and PD-L2 are predominantly non-isotype switched and can be efficiently recruited into germinal centers (GCs) in secondary responses. In contrast, a CD80 and PD-L2 positive subset arises predominantly from GCs and can quickly differentiate into antibody-secreting plasma cells (PCs). Here we demonstrate that single transient acquisition of Ag by B cells may be sufficient for their long-term participation in GC responses and for development of various memory B cell subsets including CD80 and PD-L2 positive effector-like memory cells that rapidly differentiate into class-switched PCs during recall responses.
[Mh] Termos MeSH primário: Subpopulações de Linfócitos B/imunologia
Linfócitos B/imunologia
Diferenciação Celular/fisiologia
Memória Imunológica
[Mh] Termos MeSH secundário: Animais
Subpopulações de Linfócitos B/metabolismo
Linfócitos B/metabolismo
Antígeno B7-1/metabolismo
Centro Germinativo/imunologia
Switching de Imunoglobulina
Masculino
Camundongos
Plasmócitos/imunologia
Plasmócitos/metabolismo
Proteína 2 Ligante de Morte Celular Programada 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B7-1 Antigen); 0 (Programmed Cell Death 1 Ligand 2 Protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170830
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0183877


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[PMID]:28768724
[Au] Autor:McKay JT; Haro MA; Daly CA; Yammani RD; Pang B; Swords WE; Haas KM
[Ad] Endereço:Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC 27157.
[Ti] Título:PD-L2 Regulates B-1 Cell Antibody Production against Phosphorylcholine through an IL-5-Dependent Mechanism.
[So] Source:J Immunol;199(6):2020-2029, 2017 Sep 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:B-1 cells produce natural Abs which provide an integral first line of defense against pathogens while also performing important homeostatic housekeeping functions. In this study, we demonstrate that programmed cell death 1 ligand 2 (PD-L2) regulates the production of natural Abs against phosphorylcholine (PC). Naive PD-L2-deficient (PD-L2 ) mice produced significantly more PC-reactive IgM and IgA. This afforded PD-L2 mice with selectively enhanced protection against PC-expressing nontypeable , but not PC-negative nontypeable , relative to wild-type mice. PD-L2 mice had significantly increased PC-specific CD138 splenic plasmablasts bearing a B-1a phenotype, and produced PC-reactive Abs largely of the T15 Id. Importantly, PC-reactive B-1 cells expressed PD-L2 and irradiated chimeras demonstrated that B cell-intrinsic PD-L2 expression regulated PC-specific Ab production. In addition to increased PC-specific IgM, naive PD-L2 mice and irradiated chimeras reconstituted with PD-L2 B cells had significantly higher levels of IL-5, a potent stimulator of B-1 cell Ab production. PD-L2 mAb blockade of wild-type B-1 cells in culture significantly increased CD138 and Blimp1 expression and PC-specific IgM, but did not affect proliferation. PD-L2 mAb blockade significantly increased IL-5 T cells in culture. Both IL-5 neutralization and STAT5 inhibition blunted the effects of PD-L2 mAb blockade on B-1 cells. Thus, B-1 cell-intrinsic PD-L2 expression inhibits IL-5 production by T cells and thereby limits natural Ab production by B-1 cells. These findings have broad implications for the development of therapeutic strategies aimed at altering natural Ab levels critical for protection against infectious disease, autoimmunity, allergy, cancer, and atherosclerosis.
[Mh] Termos MeSH primário: Formação de Anticorpos
Linfócitos B/imunologia
Imunoglobulina M/metabolismo
Fosforilcolina/imunologia
Proteína 2 Ligante de Morte Celular Programada 1/metabolismo
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Anticorpos Bloqueadores/farmacologia
Diferenciação Celular
Proliferação Celular
Células Cultivadas
Homeostase
Imunidade Inata
Interleucina-5/metabolismo
Ativação Linfocitária
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fator 1 de Ligação ao Domínio I Regulador Positivo
Proteína 2 Ligante de Morte Celular Programada 1/imunologia
Sindecana-1/genética
Sindecana-1/metabolismo
Fatores de Transcrição/genética
Fatores de Transcrição/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Blocking); 0 (Immunoglobulin M); 0 (Interleukin-5); 0 (Pdcd1lg2 protein, mouse); 0 (Prdm1 protein, mouse); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Syndecan-1); 0 (Transcription Factors); 107-73-3 (Phosphorylcholine); EC 2.1.1.- (Positive Regulatory Domain I-Binding Factor 1)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170804
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1700555


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[PMID]:28701512
[Au] Autor:Bellora F; Dondero A; Corrias MV; Casu B; Regis S; Caliendo F; Moretta A; Cazzola M; Elena C; Vinti L; Locatelli F; Bottino C; Castriconi R
[Ad] Endereço:Dipartimento di Medicina Sperimentale, Università degli Studi di Genova, 16132 Genoa, Italy.
[Ti] Título:Imatinib and Nilotinib Off-Target Effects on Human NK Cells, Monocytes, and M2 Macrophages.
[So] Source:J Immunol;199(4):1516-1525, 2017 Aug 15.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematological neoplasms. Moreover, in solid tumors such as stage 4 neuroblastomas (NB), imatinib showed benefits that might depend on both on-target and immunological off-target effects. We investigated the effects of imatinib and nilotinib on human NK cells, monocytes, and macrophages. High numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients. Conversely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunostimulatory cytokines, and degranulated in the presence of NB cells. In NB, neither drug reduced the expression of ligands for activating NK receptors or upregulated that of HLA class I, B7-H3, PD-L1, and PD-L2, molecules that might limit NK cell function. Interestingly, TKIs modulated the chemokine receptor repertoire of immune cells. Acting at the transcriptional level, they increased the surface expression of CXCR4, an effect observed also in NK cells and monocytes of patients receiving imatinib for chronic myeloid leukemia. Moreover, TKIs reduced the expression of CXCR3 (in NK cells) and CCR1 (in monocytes). Monocytes also decreased the expression of M-CSFR, and low numbers of cells underwent differentiation toward macrophages. M0 and M2 macrophages were highly resistant to TKIs and maintained their phenotypic and functional characteristics. Importantly, also in the presence of TKIs, the M2 immunosuppressive polarization was reverted by TLR engagement, and M1-oriented macrophages fully activated autologous NK cells. Our results contribute to better interpreting the off-target efficacy of TKIs in tumors and to envisaging strategies aimed at facilitating antitumor immune responses.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Mesilato de Imatinib/farmacologia
Células Matadoras Naturais/efeitos dos fármacos
Macrófagos/efeitos dos fármacos
Monócitos/efeitos dos fármacos
Pirimidinas/farmacologia
[Mh] Termos MeSH secundário: Antígeno B7-H1/genética
Antígeno B7-H1/metabolismo
Diferenciação Celular/efeitos dos fármacos
Citocinas/imunologia
Citocinas/secreção
Seres Humanos
Células Matadoras Naturais/imunologia
Células Matadoras Naturais/fisiologia
Ativação Linfocitária/efeitos dos fármacos
Macrófagos/imunologia
Macrófagos/fisiologia
Monócitos/imunologia
Monócitos/fisiologia
Neuroblastoma/imunologia
Proteína 2 Ligante de Morte Celular Programada 1/genética
Proteína 2 Ligante de Morte Celular Programada 1/metabolismo
Receptores CCR1/genética
Receptores CCR1/imunologia
Receptores CCR1/metabolismo
Receptores CXCR3/genética
Receptores CXCR3/metabolismo
Receptores CXCR4/genética
Receptores CXCR4/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (4-methyl-N-(3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)phenyl)-3-((4-pyridin-3-ylpyrimidin-2-yl)amino)benzamide); 0 (Antineoplastic Agents); 0 (B7-H1 Antigen); 0 (CCR1 protein, human); 0 (CD274 protein, human); 0 (CXCR3 protein, human); 0 (CXCR4 protein, human); 0 (Cytokines); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Pyrimidines); 0 (Receptors, CCR1); 0 (Receptors, CXCR3); 0 (Receptors, CXCR4); 8A1O1M485B (Imatinib Mesylate)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170714
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601695


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[PMID]:28605599
[Au] Autor:Bu LL; Yu GT; Wu L; Mao L; Deng WW; Liu JF; Kulkarni AB; Zhang WF; Zhang L; Sun ZJ
[Ad] Endereço:1 The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan, China.
[Ti] Título:STAT3 Induces Immunosuppression by Upregulating PD-1/PD-L1 in HNSCC.
[So] Source:J Dent Res;96(9):1027-1034, 2017 Aug.
[Is] ISSN:1544-0591
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Head and neck cancer is one of the most prevalent cancers around the world. Head and neck squamous cell carcinoma (HNSCC) accounts for nearly 90% of head and neck cancer. In recent years, significant advances have been made in immunotherapy for HNSCC. Although some clinical trials targeting immune checkpoints have shown success, the molecular mechanism for regulation of programmed death 1 (PD-1) and its ligand (PD-L1) is partially understood. In an effort to explore the effect of activation of signal transducers and activators of transcriptions (STAT3) on PD-1/PD-L1, the expression and correlation between phosphorylation of STAT3 and PD-1/PD-L1 were determined with immunostaining of human and mouse HNSCC tissue sections. PD-1/PD-L1 overexpression was found to be significantly associated with p-STAT3 in human and mouse HNSCC. Targeting STAT3 by a small molecule effectively inhibited the expression of PD-L1 in the CAL27 cell line. Furthermore, we found that blockade of STAT3 signaling downregulated PD-1/PD-L1 in a Tgfbr1/Pten 2cKO HNSCC mouse model. These findings suggest that STAT3 signaling plays an important role in PD-1/PD-L1 regulation and the antitumor immune response of HNSCC.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/imunologia
Neoplasias de Cabeça e Pescoço/imunologia
Proteína 2 Ligante de Morte Celular Programada 1/metabolismo
Fator de Transcrição STAT3/imunologia
[Mh] Termos MeSH secundário: Animais
Western Blotting
Células Cultivadas
Citometria de Fluxo
Seres Humanos
Imuno-Histoquímica
Camundongos
Transdução de Sinais
Análise Serial de Tecidos
Ativação Transcricional
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (PDCD1LG2 protein, human); 0 (Pdcd1lg2 protein, mouse); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (STAT3 Transcription Factor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170918
[Lr] Data última revisão:
170918
[Sb] Subgrupo de revista:D; IM
[Da] Data de entrada para processamento:170613
[St] Status:MEDLINE
[do] DOI:10.1177/0022034517712435


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[PMID]:28570665
[Au] Autor:Hirose T; Tanaka Y; Tanaka A; Sakai H; Sasaki Y; Shinohara N; Ohdan H
[Ad] Endereço:Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
[Ti] Título:PD-L1/PD-L2-expressing B-1 cells inhibit alloreactive T cells in mice.
[So] Source:PLoS One;12(6):e0178765, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:B cells constitute a complex system of antigen-presenting cells (APCs) and exist as distinct subsets that differ in their lineage affiliation, surface molecule expression, and biological function, thus potentially regulating the immune response. In this study, we investigated the immune-regulatory roles of murine B cell subsets as regulatory APCs targeting alloreactive T cells. Either splenic B cells, peritoneal cavity (PerC) B cells, or non-B cells from Balb/c mice were intravenously injected into B6 mice. Serum levels of anti-Balb/c antibodies in the recipients of PerC B cells were significantly lower than those in the recipients of splenic B cells and PerC non-B cells, as determined over a 4-week period after the injection. Mixed-lymphocyte reaction (MLR) assays using splenocytes from the B6 mice at 2 weeks after the injection revealed the significantly reduced anti-Balb/c T cell-responses in the recipients of PerC B cells, as compared to those in the recipients of splenic B cells or untreated control mice. Since PerC B cells contained MHC class II+ CD80+ CD86+ PD-L1+ PD-L2+ cells among the CD5+ B-1a cell subset, PerC B cells from Balb/c mice were pre-incubated with anti-PD-L1/PD-L2 mAbs prior to injection. This treatment abrogated their immune-regulatory effects on anti-Balb/c T cells in the MLR assays. In addition, the inoculation with Balb/c PerC B cells significantly prolonged the survival of subsequently grafted Balb/c hearts in B6 mouse recipients, whereas that with SPL B cells did not. These findings indicate that the PerC B cells, including PD-L1/PD-L2 B-1a cells, may suppress T cells responding to allostimulation, and thus may be optimal for donor lymphocyte injection.
[Mh] Termos MeSH primário: Antígeno B7-H1/metabolismo
Proteína 2 Ligante de Morte Celular Programada 1/metabolismo
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Camundongos
Camundongos Endogâmicos BALB C
Camundongos Endogâmicos C57BL
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (Cd274 protein, mouse); 0 (Pdcd1lg2 protein, mouse); 0 (Programmed Cell Death 1 Ligand 2 Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178765


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[PMID]:28556548
[Au] Autor:Fukasawa T; Yoshizaki A; Ebata S; Nakamura K; Saigusa R; Miura S; Yamashita T; Hirabayashi M; Ichimura Y; Taniguchi T; Asano Y; Shimizu H; Kazoe Y; Mawatari K; Kitamori T; Sato S
[Ad] Endereço:The University of Tokyo, Tokyo, Japan.
[Ti] Título:Contribution of Soluble Forms of Programmed Death 1 and Programmed Death Ligand 2 to Disease Severity and Progression in Systemic Sclerosis.
[So] Source:Arthritis Rheumatol;69(9):1879-1890, 2017 Sep.
[Is] ISSN:2326-5205
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To determine the function and serum levels of soluble forms of programmed death 1 (sPD-1) and one of its ligands, soluble PD ligand 2 (sPD-L2), in patients with systemic sclerosis (SSc) and in a mouse model of topoisomerase I (topo I)-induced SSc. METHODS: Serum levels of sPD-1 and sPD-L2 in 91 patients with SSc were examined by enzyme-linked immunosorbent assay (ELISA). Expression of PD-1 and PD-L2 on T cells, B cells, and macrophages was quantified by flow cytometry. The effects of blockade of PD-1 and PD-L2 were analyzed by microfluidic ELISA (micro-ELISA), a technique that can measure very low amounts of cytokines. In addition, the effects of sPD-1 and sPD-L2 on disease progression were assessed in mice with topo I-induced SSc. RESULTS: Serum levels of sPD-1 and sPD-L2 were elevated in patients with SSc and correlated with the extent of fibrosis and immunologic abnormalities. Expression levels of PD-1 and PD-L2 were significantly elevated on SSc T cells, B cells, and macrophages. Micro-ELISA analysis of serum samples from patients with SSc showed that PD-L2 B cells had higher levels of interleukin-10 (IL-10) production compared with PD-L2 B cells, indicating that PD-L2 acts as a regulator of T cell cytokine production via cognate interactions with T cells and B cells. In mice with topo I-induced SSc, production of IL-10 by topo I-specific B cells in cultures with T cells and topo I protein was significantly higher than that by conventional B cells, and intraperitoneal injection of recombinant chimeric PD-1-Fc and PD-L2-Fc canceled these enhanced effects. CONCLUSION: These results suggest that sPD-1 and sPD-L2 contribute to disease development in SSc via the regulation of cognate interactions with T cells and B cells.
[Mh] Termos MeSH primário: Proteína 2 Ligante de Morte Celular Programada 1/sangue
Receptor de Morte Celular Programada 1/sangue
Escleroderma Sistêmico/sangue
[Mh] Termos MeSH secundário: Adulto
Animais
Linfócitos B/metabolismo
DNA Topoisomerases Tipo I
Progressão da Doença
Ensaio de Imunoadsorção Enzimática
Feminino
Citometria de Fluxo
Seres Humanos
Macrófagos/metabolismo
Masculino
Camundongos
Meia-Idade
Escleroderma Sistêmico/etiologia
Escleroderma Sistêmico/patologia
Índice de Gravidade de Doença
Linfócitos T/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Programmed Cell Death 1 Receptor); EC 5.99.1.2 (DNA Topoisomerases, Type I)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170921
[Lr] Data última revisão:
170921
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE
[do] DOI:10.1002/art.40164


  8 / 336 MEDLINE  
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[PMID]:28488345
[Au] Autor:Pinto N; Park JR; Murphy E; Yearley J; McClanahan T; Annamalai L; Hawkins DS; Rudzinski ER
[Ad] Endereço:Division of Hematology/Oncology, Seattle Children's Hospital, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington.
[Ti] Título:Patterns of PD-1, PD-L1, and PD-L2 expression in pediatric solid tumors.
[So] Source:Pediatr Blood Cancer;64(11), 2017 Nov.
[Is] ISSN:1545-5017
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Significant antitumor effects have been observed in a variety of malignancies via blockade of immune checkpoints. Interaction of programmed death 1 (PD-1) with its ligands PD-L1 and PD-L2 suppresses T-cell function and restricts immune-mediated tumor killing. We examined expression of these proteins in children with solid tumors, as expression may serve as biomarkers of response to this class of drugs. METHODS: Sections cut from formalin-fixed paraffin-embedded (FFPE) tissue blocks were processed and evaluated for PD-1, PD-L1, and PD-L2 by immunohistochemistry (IHC) as well as by mRNA expression. A semiquantitative 0-5 IHC scoring system (0 = negative to 5 = very high) was applied, with scores incorporating combined prevalence of tumor cell and nontumor cell labeling. Expression profiling was performed using the NanoString nCounter™ system. Data analysis was performed using quantile normalization. All quantile-normalized data underwent subsequent log10 transformation. RESULTS: One hundred twenty-four FFPE blocks were included in the analysis. PD-1, PD-L1, and PD-L2 IHC were not evaluable in 8, 0, and 12 blocks, respectively. PD-1, PDL-1, and PDL-2 expression was negative to moderate by both IHC (range 0-3) and mRNA expression (range 0-2.62). Correlation between IHC score and mRNA expression was poor for all three tested proteins (PD-1, r = 0.06; PDL-1, r = 0.007; and PDL-2, r = 0.15). CONCLUSIONS: Expression of PD-1, PD-L1, and PD-L2 is low in pediatric solid tumors. At low levels of expression, IHC score and mRNA expression correlate poorly. Current and planned clinical trials will determine whether this low level of expression predicts limited response to immune checkpoint inhibitors.
[Mh] Termos MeSH primário: Antígeno B7-H1/metabolismo
Biomarcadores Tumorais/metabolismo
Neoplasias/metabolismo
Proteína 2 Ligante de Morte Celular Programada 1/metabolismo
Receptor de Morte Celular Programada 1/metabolismo
[Mh] Termos MeSH secundário: Antígeno B7-H1/genética
Biomarcadores Tumorais/genética
Criança
Seres Humanos
Técnicas Imunoenzimáticas
Estadiamento de Neoplasias
Neoplasias/patologia
Prognóstico
Proteína 2 Ligante de Morte Celular Programada 1/genética
Receptor de Morte Celular Programada 1/genética
RNA Mensageiro/análise
RNA Mensageiro/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD274 protein, human); 0 (PDCD1 protein, human); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Programmed Cell Death 1 Receptor); 0 (RNA, Messenger)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1002/pbc.26613


  9 / 336 MEDLINE  
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[PMID]:28436955
[Au] Autor:Gundra UM; Girgis NM; Gonzalez MA; San Tang M; Van Der Zande HJP; Lin JD; Ouimet M; Ma LJ; Poles J; Vozhilla N; Fisher EA; Moore KJ; Loke P
[Ad] Endereço:Department of Microbiology, New York University School of Medicine, New York, New York, USA.
[Ti] Título:Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation.
[So] Source:Nat Immunol;18(6):642-653, 2017 Jun.
[Is] ISSN:1529-2916
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:It remains unclear whether activated inflammatory macrophages can adopt features of tissue-resident macrophages, or what mechanisms might mediate such a phenotypic conversion. Here we show that vitamin A is required for the phenotypic conversion of interleukin 4 (IL-4)-activated monocyte-derived F4/80 CD206 PD-L2 MHCII macrophages into macrophages with a tissue-resident F4/80 CD206 PD-L2 MHCII UCP1 phenotype in the peritoneal cavity of mice and during the formation of liver granulomas in mice infected with Schistosoma mansoni. The phenotypic conversion of F4/80 CD206 macrophages into F4/80 CD206 macrophages was associated with almost complete remodeling of the chromatin landscape, as well as alteration of the transcriptional profiles. Vitamin A-deficient mice infected with S. mansoni had disrupted liver granuloma architecture and increased mortality, which indicates that failure to convert macrophages from the F4/80 CD206 phenotype to F4/80 CD206 may lead to dysregulated inflammation during helminth infection.
[Mh] Termos MeSH primário: Granuloma/imunologia
Fígado/imunologia
Macrófagos/imunologia
Esquistossomose mansoni/imunologia
Deficiência de Vitamina A/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos de Diferenciação/metabolismo
Citometria de Fluxo
Antígenos de Histocompatibilidade Classe II/metabolismo
Interleucina-4/imunologia
Lectinas Tipo C/metabolismo
Fígado/patologia
Macrófagos/efeitos dos fármacos
Macrófagos/metabolismo
Macrófagos Alveolares/efeitos dos fármacos
Macrófagos Alveolares/imunologia
Macrófagos Alveolares/metabolismo
Lectinas de Ligação a Manose/metabolismo
Camundongos
Cavidade Peritoneal/citologia
Proteína 2 Ligante de Morte Celular Programada 1/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Receptores de Superfície Celular/metabolismo
Schistosoma mansoni
Esquistossomose mansoni/patologia
Tretinoína/farmacologia
Proteína Desacopladora 1/metabolismo
Vitaminas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antigens, Differentiation); 0 (Histocompatibility Antigens Class II); 0 (Lectins, C-Type); 0 (Mannose-Binding Lectins); 0 (Pdcd1lg2 protein, mouse); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Receptors, Cell Surface); 0 (Ucp1 protein, mouse); 0 (Uncoupling Protein 1); 0 (Vitamins); 0 (mannose receptor); 0 (monocyte-macrophage differentiation antigen); 207137-56-2 (Interleukin-4); 5688UTC01R (Tretinoin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170425
[St] Status:MEDLINE
[do] DOI:10.1038/ni.3734


  10 / 336 MEDLINE  
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[PMID]:28432450
[Au] Autor:Kitamura Y; Sasaki H; Yoshida K
[Ad] Endereço:Department of Neurosurgery, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. ykita@sc4.so-net.ne.jp.
[Ti] Título:Genetic aberrations and molecular biology of skull base chordoma and chondrosarcoma.
[So] Source:Brain Tumor Pathol;34(2):78-90, 2017 Apr.
[Is] ISSN:1861-387X
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:Chordomas and chondrosarcomas are two major malignant bone neoplasms located at the skull base. These tumors are rarely metastatic, but can be locally invasive and resistant to conventional chemotherapies and radiotherapies. Accordingly, therapeutic approaches for the treatment of these tumors can be difficult. Additionally, their location at the skull base makes them problematic. Although accurate diagnosis of these tumors is important because of their distinct prognoses, distinguishing between these tumor types is difficult due to overlapping radiological and histopathological findings. However, recent accumulation of molecular and genetic studies, including extracranial location analysis, has provided us clues for accurate diagnosis. In this report, we review the genetic aberrations and molecular biology of these two tumor types. Among the abundant genetic features of these tumors, brachyury immunohistochemistry and direct sequencing of IDH1/2 are simple and useful techniques that can be used to distinguish between these tumors. Although it is still unclear why these tumors, which have such distinct genetic backgrounds, show similar histopathological findings, comparison of their genetic backgrounds could provide essential information.
[Mh] Termos MeSH primário: Condrossarcoma/genética
Cordoma/genética
Isocitrato Desidrogenase/genética
Mutação
Neoplasias da Base do Crânio/genética
[Mh] Termos MeSH secundário: Antígeno B7-H1
Condrossarcoma/diagnóstico
Condrossarcoma/imunologia
Condrossarcoma/terapia
Cordoma/diagnóstico por imagem
Cordoma/imunologia
Cordoma/terapia
Diagnóstico Diferencial
Proteínas Fetais/genética
Seres Humanos
Imuno-Histoquímica
Terapia de Alvo Molecular
Proteína 2 Ligante de Morte Celular Programada 1
Análise de Sequência de DNA
Neoplasias da Base do Crânio/diagnóstico
Neoplasias da Base do Crânio/imunologia
Neoplasias da Base do Crânio/terapia
Proteínas com Domínio T-Box/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (Brachyury protein); 0 (CD274 protein, human); 0 (Fetal Proteins); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (T-Box Domain Proteins); EC 1.1.1.41 (Isocitrate Dehydrogenase); EC 1.1.1.41 (isocitrate dehydrogenase 2, human); EC 1.1.1.42. (IDH1 protein, human)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170423
[St] Status:MEDLINE
[do] DOI:10.1007/s10014-017-0283-y



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