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[PMID]: 29268133 [Au] Autor: Zhu G; Xu Y; Cen X; Nandakumar KS; Liu S; Cheng K [Ad] Endereço: Guangdong Provincial Key Laboratory of New Drug Screening and Guangzhou Key Laboratory of Drug Research for Emerging Virus Prevention and Treatment, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China. [Ti] Título: Targeting pattern-recognition receptors to discover new small molecule immune modulators. [So] Source: Eur J Med Chem;144:82-92, 2018 Jan 20. [Is] ISSN: 1768-3254 [Cp] País de publicação: France [La] Idioma: eng [Ab] Resumo: Pattern recognition receptors (PRRs) are key immune receptors of the innate immune system, which recognize the conserved pathogen-associated molecular patterns (PAMPs) of the invading pathogens. Compared to the adaptive immune receptors, PRRs have three distinguishing features, viz., universal expression, fast response and recognizing many kinds of microbes. Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and NOD-like receptors (NLRs) recognize viral nucleic acid/bacterial fragments and trigger anti-microbial innate immune responses. Upon recognition of their ligand species, PRRs recruit specific intracellular adaptor proteins to initiate signaling pathways culminating in the activation of nuclear factor-κB (NF-κB), mitogen-activated protein (MAP) kinases and interferon regulatory factors (IRFs) that control the transcription of genes encoding pro-inflammatory factors including type I interferon and other inflammatory cytokines, which are critical for eliminating the potential threat to the host. Here, we summarize the effects of small molecule regulators acting on signaling pathways initiated by TLR, RLR and NLR as well as their influence on innate and adaptive immune responses leading to therapy. [Mh] Termos MeSH primário: Imunidade Adaptativa/efeitos dos fármacos Imunidade Inata/efeitos dos fármacos Fatores Imunológicos/química Fatores Imunológicos/farmacologia Receptores de Reconhecimento de Padrão/imunologia [Mh] Termos MeSH secundário: Animais Descoberta de Drogas Seres Humanos Inflamação/tratamento farmacológico Inflamação/imunologia Terapia de Alvo Molecular Bibliotecas de Moléculas Pequenas/química Bibliotecas de Moléculas Pequenas/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Immunologic Factors); 0 (Receptors, Pattern Recognition); 0 (Small Molecule Libraries) [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: 171222 [St] Status: MEDLINE

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[PMID]: 28465096 [Au] Autor: Nicoli F; Appay V [Ad] Endereço: Sorbonne Universités, UPMC Univ Paris 06, DHU FAST, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), F-75013 Paris, France; INSERM, U1135, CIMI-Paris, F-75013 Paris, France. Electronic address: nclfnc1@unife.it. [Ti] Título: Immunological considerations regarding parental concerns on pediatric immunizations. [So] Source: Vaccine;35(23):3012-3019, 2017 05 25. [Is] ISSN: 1873-2518 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Despite the fundamental role of vaccines in the decline of infant mortality, parents may decide to decline vaccination for their own children. Many factors may influence this decision, such as the belief that the infant immune system is weakened by vaccines, and concerns have been raised about the number of vaccines and the early age at which they are administered. Studies focused on the infant immune system and its reaction to immunizations, summarized in this review, show that vaccines can overcome those suboptimal features of infant immune system that render them more at risk of infections and of their severe manifestations. In addition, many vaccines have been shown to improve heterologous innate and adaptive immunity resulting in lower mortality rates for fully vaccinated children. Thus, multiple vaccinations are necessary and not dangerous, as infants can respond to several antigens as well as when responding to single stimuli. Current immunization schedules have been developed and tested to avoid vaccine interference, improve benefits and reduce side effects compared to single administrations. The infant immune system is therefore capable, early after birth, of managing several antigenic challenges and exploits them to prompt its development. [Mh] Termos MeSH primário: Imunização/psicologia Pais/psicologia Vacinas/imunologia [Mh] Termos MeSH secundário: Imunidade Adaptativa Criança Conhecimentos, Atitudes e Prática em Saúde Seres Humanos Imunidade Inata Imunização/efeitos adversos Esquemas de Imunização Lactente Mortalidade Infantil Vacinas/administração & dosagem [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Vaccines) [Em] Mês de entrada: 1802 [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

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[PMID]: 28747424 [Au] Autor: Schwartz C; Khan AR; Floudas A; Saunders SP; Hams E; Rodewald HR; McKenzie ANJ; Fallon PG [Ad] Endereço: Trinity Biomedical Sciences Institute, School of Medicine, Trinity College Dublin, Dublin, Ireland. [Ti] Título: ILC2s regulate adaptive Th2 cell functions via PD-L1 checkpoint control. [So] Source: J Exp Med;214(9):2507-2521, 2017 Sep 04. [Is] ISSN: 1540-9538 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Group 2 innate lymphoid cells (ILC2s) are important effector cells driving the initiation of type 2 immune responses leading to adaptive T helper 2 (Th2) immunity. Here we show that ILC2s dynamically express the checkpoint inhibitor molecule PD-L1 during type 2 pulmonary responses. Surprisingly, PD-L1:PD-1 interaction between ILC2s and CD4 T cells did not inhibit the T cell response, but PD-L1-expressing ILC2s stimulated increased expression of GATA3 and production of IL-13 by Th2 cells both in vitro and in vivo. Conditional deletion of PD-L1 on ILC2s impaired early Th2 polarization and cytokine production, leading to delayed worm expulsion during infection with the gastrointestinal helminth Our results identify a novel PD-L1-controlled mechanism for type 2 polarization, with ILC2s mediating an innate checkpoint to control adaptive T helper responses, which has important implications for the treatment of type 2 inflammation. [Mh] Termos MeSH primário: Antígeno B7-H1/fisiologia Linfócitos/fisiologia Células Th2/fisiologia [Mh] Termos MeSH secundário: Imunidade Adaptativa/imunologia Imunidade Adaptativa/fisiologia Animais Antígeno B7-H1/imunologia Fator de Transcrição GATA3/fisiologia Imunidade Celular/imunologia Imunidade Celular/fisiologia Interleucina-13/fisiologia Linfócitos/imunologia Camundongos Camundongos Endogâmicos C57BL Nippostrongylus/imunologia Infecções por Strongylida/imunologia Células Th2/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (B7-H1 Antigen); 0 (Cd274 protein, mouse); 0 (GATA3 Transcription Factor); 0 (Gata3 protein, mouse); 0 (Interleukin-13) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 180305 [Lr] Data última revisão: 180305 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170728 [St] Status: MEDLINE [do] DOI: 10.1084/jem.20170051

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[PMID]: 29324830 [Au] Autor: Skeate JG; Da Silva DM; Chavez-Juan E; Anand S; Nuccitelli R; Kast WM [Ad] Endereço: Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, CA, United States of America. [Ti] Título: Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response. [So] Source: PLoS One;13(1):e0191311, 2018. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Nano-Pulse Stimulation (NPS) is a non-thermal pulsed electric field modality that has been shown to have cancer therapeutic effects. Here we applied NPS treatment to the human papillomavirus type 16 (HPV 16)-transformed C3.43 mouse tumor cell model and showed that it is effective at eliminating primary tumors through the induction of immunogenic cell death while subsequently increasing the number of tumor-infiltrating lymphocytes within the tumor microenvironment. In vitro NPS treatment of C3.43 cells resulted in a doubling of activated caspase 3/7 along with the translocation of phosphatidylserine (PS) to the outer leaflet of the plasma membrane, indicating programmed cell death activity. Tumor-bearing mice receiving standard NPS treatment showed an initial decrease in tumor volume followed by clearing of tumors in most mice, and a significant increase in overall survival. Intra-tumor analysis of mice that were unable to clear tumors showed an inverse correlation between the number of tumor infiltrating lymphocytes and the size of the tumor. Approximately half of the mice that cleared established tumors were protected against tumor re-challenge on the opposite flank. Selective depletion of CD8+ T cells eliminated this protection, suggesting that NPS treatment induces an adaptive immune response generating CD8+ T cells that recognize tumor antigen(s) associated with the C3.43 tumor model. This method may be utilized in the future to not only ablate primary tumors, but also to induce an anti-tumor response driven by effector CD8+ T cells capable of protecting individuals from disease recurrence. [Mh] Termos MeSH primário: Imunidade Adaptativa Morte Celular/imunologia Transformação Celular Viral Estimulação Elétrica Papillomavirus Humano 16/fisiologia [Mh] Termos MeSH secundário: Animais Antígenos CD8/metabolismo Caspase 3/metabolismo Caspase 7/metabolismo Linhagem Celular Tumoral Ativação Enzimática Seres Humanos Camundongos Nanotecnologia Carga Tumoral [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (CD8 Antigens); EC 3.4.22.- (Caspase 3); EC 3.4.22.- (Caspase 7) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180226 [Lr] Data última revisão: 180226 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180112 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0191311

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[PMID]: 29384601 [Au] Autor: Wang Y; Yao C; Ding; Li C; Wang J; Wu M; Lei Y [Ti] Título: Enhancement of the Immune Function by Titanium Dioxide Nanorods and Their Application in Cancer Immunotherapy. [So] Source: J Biomed Nanotechnol;13(4):367-80, 2017 Apr. [Is] ISSN: 1550-7033 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: With the rapid development of nanotherapy, concerns surrounding the possible use of nanomaterials-mediated immunomodulation are growing. Thus, evaluating the effects of novel materials for potential application in nanotherapy is essential. Herein, we studied the effects of TiO2-nanorods (NRs) on the immune function and their potential application in immunotherapy. TiO2-NRs exerted specific immunomodulatory effects on the main immune cells. Cytokines TNF-α and IL-2, which play a key role in antitumor processes, were upregulated more significantly than other cytokines (IL-4, IL-5, IFN-γ) in the main immune cells. The cells group treated with a high dose of TiO2-NRs (50 mg/L) for 12 h produced a higher TNF-α content of 530.4 pg/mL relative to that (238.2 pg/mL) treated with saline solution only. The TNF-α content increased to 2.2- and 4.9-fold for macrophages and lymphocytes, respectively. Also, we conclude that TiO2-NRs exposure may trigger T cell proliferation and bias toward Th1 immune response and cause a long-lasting activation of lymphocytes involved in adaptive immunity rather than an innate immunity in BALB/c mice. Furthermore, we explored the potential application of TiO2-NRs in immunotherapy. At a given dose of 1 mg/kg, the inhibition rate by TiO2-NRs (26.7%) was much higher than that by DOX (13.3%). [Mh] Termos MeSH primário: Imunidade Adaptativa/efeitos dos fármacos Nanotubos/química Neoplasias Experimentais/imunologia Neoplasias Experimentais/terapia Titânio/administração & dosagem Titânio/imunologia [Mh] Termos MeSH secundário: Imunidade Adaptativa/imunologia Animais Linhagem Celular Tumoral Citocinas/imunologia Relação Dose-Resposta a Droga Feminino Imunoterapia/métodos Camundongos Camundongos Endogâmicos BALB C Nanotubos/ultraestrutura Neoplasias Experimentais/patologia Titânio/química Resultado do Tratamento [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Cytokines); 15FIX9V2JP (titanium dioxide); D1JT611TNE (Titanium) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180223 [Lr] Data última revisão: 180223 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180201 [St] Status: MEDLINE

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[PMID]: 29254286 [Au] Autor: Robuffo I; Toniato E; Tettamanti L; Mastrangelo F; Ronconi G; Frydas I; Caraffa A; Kritas SK; Conti P [Ad] Endereço: Institute of Molecular Genetics, CNR, Sede di Chieti, Italy. [Ti] Título: Mast cell in innate immunity mediated by proinflammatory and antiinflammatory IL-1 family members. [So] Source: J Biol Regul Homeost Agents;31(4):837-842, 2017 Oct-Dec. [Is] ISSN: 0393-974X [Cp] País de publicação: Italy [La] Idioma: eng [Ab] Resumo: Innate immunity consists of physical and chemical barriers which provide the early defense against infections. Innate immunity orchestrates the defense of the host with cellular and biochemical proteins. Mast cells (MCs) are involved in innate and adaptive immunity and are the first line of defense which generates multiple inflammatory cytokines/chemokines in response to numerous antigens. MC-activated antigen receptor Fc-RI provokes a number of important biochemical pathways with secretion of numerous vasoactive, chemoattractant and inflammatory compounds which participate in allergic and inflammatory diseases. MCs can also be activated by Th1 cytokines and generate pre-formed and de novo inflammatory mediators, including TNF. IL-37 is an anti-inflammatory cytokine which binds IL-18R-alpha chain and reduces the production of inflammatory IL-1 family members. IL-37 down-regulates innate immunity by inhibiting macrophage response and its accumulation and reduces the cytokines that mediate inflammatory diseases. Here, we discuss the relationship between MCs, innate immunity, and pro-inflammatory and anti-inflammatory cytokines. [Mh] Termos MeSH primário: Inflamação/imunologia Interleucina-1/imunologia Macrófagos/imunologia Mastócitos/imunologia Receptores de Interleucina-1/imunologia [Mh] Termos MeSH secundário: Imunidade Adaptativa Linfócitos B/imunologia Linfócitos B/patologia Comunicação Celular Regulação da Expressão Gênica Seres Humanos Imunidade Inata Inflamação/genética Inflamação/patologia Interleucina-1/genética Subunidade alfa de Receptor de Interleucina-18/genética Subunidade alfa de Receptor de Interleucina-18/imunologia Peptídeos e Proteínas de Sinalização Intracelular/genética Peptídeos e Proteínas de Sinalização Intracelular/imunologia Macrófagos/patologia Mastócitos/patologia Receptores de Interleucina-1/genética Transdução de Sinais Linfócitos T/imunologia Linfócitos T/patologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (FcRI protein, human); 0 (IL18R1 protein, human); 0 (IL37 protein, human); 0 (Interleukin-1); 0 (Interleukin-18 Receptor alpha Subunit); 0 (Intracellular Signaling Peptides and Proteins); 0 (Receptors, Interleukin-1) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180222 [Lr] Data última revisão: 180222 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171220 [St] Status: MEDLINE

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[PMID]: 27779499 [Au] Autor: Choy MC; Visvanathan K; De Cruz P [Ad] Endereço: *Department of Gastroenterology, The Austin Hospital, Melbourne, Australia; †Department of Gastroenterology, St Vincent's Hospital, Melbourne, Australia; ‡Department of Medicine, Austin Academic Centre, University of Melbourne, Melbourne, Australia; and §Department of Medicine, Eastern Hill Academic Centre, University of Melbourne, Melbourne, Australia. [Ti] Título: An Overview of the Innate and Adaptive Immune System in Inflammatory Bowel Disease. [So] Source: Inflamm Bowel Dis;23(1):2-13, 2017 Jan. [Is] ISSN: 1536-4844 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Inflammatory bowel diseases (IBDs) are thought to develop as a result of complex interactions between host genetics, the immune system and the environment including the gut microbiome. Although an improved knowledge of the immunopathogenesis of IBDs has led to great advances in therapy such as the highly effective anti-tumor necrosis factor class of medications, a significant proportion of patients with Crohn's disease and ulcerative colitis do not respond to anti-tumor necrosis factor antibodies. Further understanding of the different immune pathways involved in the genesis of chronic intestinal inflammation is required to help find effective treatments for IBDs. In this review, the role of the mucosal innate and adaptive immune system in IBD is summarized, highlighting new areas of discovery which may hold the key to identifying novel predictive or prognostic biomarkers and new avenues of therapeutic discovery. [Mh] Termos MeSH primário: Imunidade Adaptativa Colite Ulcerativa/imunologia Doença de Crohn/imunologia Imunidade Inata [Mh] Termos MeSH secundário: Seres Humanos Mucosa Intestinal/imunologia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180220 [Lr] Data última revisão: 180220 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161026 [St] Status: MEDLINE [do] DOI: 10.1097/MIB.0000000000000955

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[PMID]: 29343712 [Au] Autor: Hirsch AJ; Roberts VHJ; Grigsby PL; Haese N; Schabel MC; Wang X; Lo JO; Liu Z; Kroenke CD; Smith JL; Kelleher M; Broeckel R; Kreklywich CN; Parkins CJ; Denton M; Smith P; DeFilippis V; Messer W; Nelson JA; Hennebold JD; Grafe M; Colgin L; Lewis A; Ducore R; Swanson T; Legasse AW; Axthelm MK; MacAllister R; Moses AV; Morgan TK; Frias AE; Streblow DN [Ad] Endereço: The Vaccine & Gene Institute, Oregon Health and Science University (OHSU), 505 NW 185th Ave, Beaverton, 97006, USA. hirschal@ohsu.edu. [Ti] Título: Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. [So] Source: Nat Commun;9(1):263, 2018 01 17. [Is] ISSN: 2041-1723 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal growth restriction and fetal central nervous system malformations, which are outcomes broadly referred to as the Congenital Zika Syndrome (CZS). Here we infect pregnant rhesus macaques and investigate the impact of persistent ZIKV infection on uteroplacental pathology, blood flow, and fetal growth and development. Despite seemingly normal fetal growth and persistent fetal-placenta-maternal infection, advanced non-invasive in vivo imaging studies reveal dramatic effects on placental oxygen reserve accompanied by significantly decreased oxygen permeability of the placental villi. The observation of abnormal oxygen transport within the placenta appears to be a consequence of uterine vasculitis and placental villous damage in ZIKV cases. In addition, we demonstrate a robust maternal-placental-fetal inflammatory response following ZIKV infection. This animal model reveals a potential relationship between ZIKV infection and uteroplacental pathology that appears to affect oxygen delivery to the fetus during development. [Mh] Termos MeSH primário: Placenta/metabolismo Circulação Placentária Complicações Infecciosas na Gravidez/imunologia Infecção pelo Zika virus/imunologia [Mh] Termos MeSH secundário: Imunidade Adaptativa Animais Encéfalo/embriologia Encéfalo/patologia Citocinas/sangue Modelos Animais de Doenças Feminino Desenvolvimento Fetal Feto/patologia Imunidade Inata Macaca mulatta Imagem por Ressonância Magnética Oxigênio/metabolismo Permeabilidade Placenta/imunologia Placenta/patologia Placenta/virologia Gravidez Complicações Infecciosas na Gravidez/metabolismo Complicações Infecciosas na Gravidez/patologia Complicações Infecciosas na Gravidez/fisiopatologia Carga Viral Infecção pelo Zika virus/metabolismo Infecção pelo Zika virus/patologia Infecção pelo Zika virus/fisiopatologia [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Cytokines); S88TT14065 (Oxygen) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180215 [Lr] Data última revisão: 180215 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180119 [St] Status: MEDLINE [do] DOI: 10.1038/s41467-017-02499-9

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[PMID]: 29309784 [Au] Autor: Bassi PB; de Araújo FF; Garcia GC; Vinícius da Silva M; Oliveira CJF; Bittar ER; de Souza Gomes M; Rodrigues do Amaral L; Costa E Silva MF; Nascentes GAN; Rodrigues Junior V; Martins-Filho OA; Araújo MSS; Bittar JFF [Ad] Endereço: Universidade de Uberaba (UNIUBE), Medicina Veterinária, Mestrado em Sanidade e Produção Animal nos Trópicos - Avenida Nenê Sabino 1697/1698, 38055-500, Uberaba, MG, Brazil. Electronic address: vet.bassi@gmail.com. [Ti] Título: Parasitological and immunological evaluation of cattle experimentally infected with Trypanosoma vivax. [So] Source: Exp Parasitol;185:98-106, 2018 Feb. [Is] ISSN: 1090-2449 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Trypanosoma vivax infection causes relevant economical impact due to high morbidity and mortality leading to negative impact on local livestock. Despite parasitological and serological methods are used for the diagnosis of T. vivax infection, gaps regarding sensitivity and specificity of these methods still represent a challenge. The present study aimed to compare the kinetics of parasitological and serological parameters in cattle experimentally infected with T. vivax along with immunophenotypic analysis of whole blood leukocytes. Based on the parasitemia profile the analysis were performed in three distinct periods, referred as pre-patent, patent and post-treatment. Distinct kinetics of anti-T. vivax IgM and IgG were observed during the pre-patent, patent and post-treatment periods. Increased levels of WC1 γδ T-cells were observed throughout the infection with strong correlations with other biomarkers observed during post-treatment period. Our findings demonstrated that there is a important participation of Monocytes:CD14 ; NK-cells:CD335 and WC1 γδ T-cells that coincide with the peak of parasitemia and also with the adaptive immunity, specially CD4 T-cells in T. vivax infection. The knowledge of the immune response is important not only for understanding the biology of the parasite in the host, but for the design of new treatment strategies for trypanosome infections. [Mh] Termos MeSH primário: Doenças dos Bovinos/imunologia Parasitemia/veterinária Trypanosoma vivax/imunologia Tripanossomíase Africana/veterinária [Mh] Termos MeSH secundário: Imunidade Adaptativa Animais Anticorpos Antiprotozoários/sangue Biomarcadores/análise Bovinos Doenças dos Bovinos/tratamento farmacológico Doenças dos Bovinos/parasitologia Diminazena/uso terapêutico Técnica Indireta de Fluorescência para Anticorpo/veterinária Imunidade Inata Imunoglobulina G/sangue Imunoglobulina M/sangue Imunofenotipagem/veterinária Leucócitos/classificação Leucócitos/imunologia Masculino Parasitemia/tratamento farmacológico Parasitemia/imunologia Parasitemia/parasitologia Distribuição Aleatória Tripanossomicidas/uso terapêutico Tripanossomíase Africana/tratamento farmacológico Tripanossomíase Africana/imunologia Tripanossomíase Africana/parasitologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antibodies, Protozoan); 0 (Biomarkers); 0 (Immunoglobulin G); 0 (Immunoglobulin M); 0 (Trypanocidal Agents); Y5G36EEA5Z (Diminazene) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180214 [Lr] Data última revisão: 180214 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 180109 [St] Status: MEDLINE

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[PMID]: 29223828 [Au] Autor: Ferris RL; Lenz HJ; Trotta AM; García-Foncillas J; Schulten J; Audhuy F; Merlano M; Milano G [Ad] Endereço: Department of Otolaryngology, University of Pittsburgh Cancer Institute, University of Pittsburgh, 5117 Centre Avenue, Suite 2.26, Pittsburgh, PA 15213, United States. Electronic address: ferrrl@UPMC.EDU. [Ti] Título: Rationale for combination of therapeutic antibodies targeting tumor cells and immune checkpoint receptors: Harnessing innate and adaptive immunity through IgG1 isotype immune effector stimulation. [So] Source: Cancer Treat Rev;63:48-60, 2018 Feb. [Is] ISSN: 1532-1967 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Immunoglobulin (Ig) G1 antibodies stimulate antibody-dependent cell-mediated cytotoxicity (ADCC). Cetuximab, an IgG1 isotype monoclonal antibody, is a standard-of-care treatment for locally advanced and recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and metastatic colorectal cancer (CRC). Here we review evidence regarding the clinical relevance of cetuximab-mediated ADCC and other immune functions and provide a biological rationale concerning why this property positions cetuximab as an ideal partner for immune checkpoint inhibitors (ICIs) and other emerging immunotherapies. We performed a nonsystematic review of available preclinical and clinical data involving cetuximab-mediated immune activity and combination approaches of cetuximab with other immunotherapies, including ICIs, in SCCHN and CRC. Indeed, cetuximab mediates ADCC activity in the intratumoral space and primes adaptive and innate cellular immunity. However, counterregulatory mechanisms may lead to immunosuppressive feedback loops. Accordingly, there is a strong rationale for combining ICIs with cetuximab for the treatment of advanced tumors, as targeting CTLA-4, PD-1, and PD-L1 can ostensibly overcome these immunosuppressive counter-mechanisms in the tumor microenvironment. Moreover, combining ICIs (or other immunotherapies) with cetuximab is a promising strategy for boosting immune response and enhancing response rates and durability of response. Cetuximab immune activity-including, but not limited to, ADCC-provides a strong rationale for its combination with ICIs or other immunotherapies to synergistically and fully mobilize the adaptive and innate immunity against tumor cells. Ongoing prospective studies will evaluate the clinical effect of these combination regimens and their immune effect in CRC and SCCHN and in other indications. [Mh] Termos MeSH primário: Imunidade Adaptativa/imunologia Citotoxicidade Celular Dependente de Anticorpos/imunologia Antineoplásicos Imunológicos/imunologia Cetuximab/imunologia Imunidade Inata/imunologia Imunoglobulina G/imunologia Neoplasias/imunologia [Mh] Termos MeSH secundário: Antineoplásicos Imunológicos/uso terapêutico Cetuximab/uso terapêutico Quimioterapia Combinada/métodos Seres Humanos Imunoterapia/métodos Neoplasias/terapia [Pt] Tipo de publicação: JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Antineoplastic Agents, Immunological); 0 (Immunoglobulin G); PQX0D8J21J (Cetuximab) [Em] Mês de entrada: 1802 [Cu] Atualização por classe: 180209 [Lr] Data última revisão: 180209 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 171211 [St] Status: MEDLINE

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1			PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2
2	and or and not		PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2
3	and or and not		PalavrasDescritor de assuntoDescritor de assunto primárioLimitesAutorPalavras do títuloPalavras do resumoIdiomaPaís de publicaçãoNome de substânciaNome de pessoa como assuntoRevistaAssunto de RevistaISSNTipo de publicaçãoIdentificador únicoMês de entradaAno de publicaçãoTexto completoAtualização por classeCategoria DeCSCategoria DeCS explodidaCategoria CID-10SubSetsPais de AfiliaçãoAfiliaçãoAfiliação 2

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