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LIM/56 - Laboratório de Investigação em Dermatologia e Imunodeficiências, Hospital das Clínicas, Faculdade de Medicina

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Agora exibindo 1 - 7 de 7
  • article 7 Citação(ões) na Scopus
    Host genetics contributes to the effectiveness of dendritic cell-based HIV immunotherapy
    (2018) REIS, Edione C.; SILVA, Lais T. da; SILVA, Wanessa C. da; RIOS, Alexandre; DUARTE, Alberto J.; OSHIRO, Telma M.; CROVELLA, Sergio; PONTILLO, Alessandra
    Systems biological analysis has recently revealed how innate immune variants as well as gut microbiota impact the individual response to immunization. HIV-infected (HIV+) patients have a worse response rate after standard vaccinations, possibly due to the immune exhaustion, increased gut permeability and microbial translocation. In the last decade, dendritic cells (DC)-based immunotherapy has been proposed as an alternative approach to control HIV plasma viral load, however clinical trials showed a heterogeneity of immunization response. Hypothesizing that host genetics may importantly affects the outcome of immunotherapy in HIV+ patients, genetic polymorphisms' distribution and gene expression modulation were analyzed in a phase I/II clinical trial of DC-based immunotherapy according to immunization response, and quality of vaccine product (DC). Polymorphisms in genes previously associated with progression of HIV infection to AIDS (i.e.: PARD3B, CCL5) contribute to a better response to immunotherapy in HIV+ individuals, possibly through a systemic effect on host immune system, but also directly on vaccine product. Genes expression profile after immunization correlates with different degrees of immune chronic activation/exhaustion of HIV+ patients (i.e. PD1, IL7RA, EOMES), but also with anti-viral response and DC quality (i.e.: APOBEC3G, IL8, PPIA), suggested that an immunocompetent individual would have a better vaccine response. These findings showed once more that host genetics can affect the response to DC-based immunotherapy in HIV+ individuals, contributing to the heterogeneity of response observed in concluded trials; and it can be used as predictor of immunization success.
  • article 2 Citação(ões) na Scopus
    Characterization of monocyte-derived dendritic cells used in immunotherapy for HIV-1-infected individuals
    (2018) SILVA, Lais Teodoro da; SILVA, Wanessa Cardoso da; ALMEIDA, Alexandre de; REIS, Denise da Silva; SANTLLO, Bruna Tereso; RIGATO, Paula Ordonhez; DUARTE, Alberto Jose da Silva; OSHIRO, Telma Miyuki
    Aims: A therapeutic vaccine based on monocyte-derived dendritic cells (MDDCs) has been shown to represent a promising strategy for the treatment of cancer and viral infections. Here, we characterized the MDDCs used as an immunogen in a clinical trial for an anti-HIV-1 therapeutic vaccine. Patients & Methods: Monocytes obtained from 17 HIV-infected individuals were differentiated into MDDCs and, after loading with autologous HIV, the cells were characterized concerning surface molecule expression, migratory and phagocytosis capacity, cytokine production and the induction of an effective cell-mediated immune response. Results: The MDDCs were able to induce antigen-specific responses in autologous CD4+ and CD8+ T lymphocytes. Conclusions: Despite a large interindividual variability, the results suggested that MDDCs present the potential to promote immune responses in vaccinated patients.
  • article 22 Citação(ões) na Scopus
    CD8+T Lymphocyte Expansion, Proliferation and Activation in Dengue Fever
    (2015) MATOS, Andreia Manso de; CARVALHO, Karina Inacio; ROSA, Daniela Santoro; VILLAS-BOAS, Lucy Santos; SILVA, Wanessa Cardoso da; RODRIGUES, Celia Luiza de Lima; OLIVEIRA, Olimpia Massae Nakasone Peel Furtado; LEVI, Jose Eduardo; ARAUJO, Evaldo Stanislau Affonso; PANNUTI, Claudio Sergio; LUNA, Expedito Jose Albuquerque; KALLAS, Esper George
    Dengue fever induces a robust immune response, including massive T cell activation. The level of T cell activation may, however, be associated with more severe disease. In this study, we explored the level of CD8+ T lymphocyte activation in the first six days after onset of symptoms during a DENV2 outbreak in early 2010 on the coast of Sao Paulo State, Brazil. Using flow cytometry we detected a progressive increase in the percentage of CD8+ T cells in 74 dengue fever cases. Peripheral blood mononuclear cells from 30 cases were thawed and evaluated using expanded phenotyping. The expansion of the CD8+ T cells was coupled with increased Ki67 expression. Cell activation was observed later in the course of disease, as determined by the expression of the activation markers CD38 and HLA-DR. This increased CD8+ T lymphocyte activation was observed in all memory subsets, but was more pronounced in the effector memory subset, as defined by higher CD38 expression. Our results show that most CD8+ T cell subsets are expanded during DENV2 infection and that the effector memory subset is the predominantly affected sub population.
  • article 21 Citação(ões) na Scopus
    Genotyping and differential expression analysis of inflammasome genes in sporadic malignant melanoma reveal novel contribution of CARD8, IL1B and IL18 in melanoma susceptibility and progression
    (2016) SILVA, Wanessa Cardoso da; OSHIRO, Telma Miyuki; SA, Daniel Coelho de; FRANCO, Dilcilea D. G. S.; NETO, Cyro Festa; PONTILLO, Alessandra
    Sporadic melanoma malignancy is correlated with constitutive secretion of IL-1 beta in transformed melanocytes suggesting the involvement of inflammasome in melanoma. Common variants in inflammasome genes are known to affect IL-1 beta expression. To investigate the contribution of inflammasome genetics in melanoma development and progression and to identify a potential prognostic marker, the distribution of selected inflammasome SNPs was analysed in a Brazilian case/control cohort of sporadic malignant melanoma (SMM) and then the expression of inflammasome components was evaluated in melanoma biopsies. Allele and gene-specific Taqman assays were implied for genotyping of case/control DNA samples and for relative expression analysis in skin biopsies respectively. CARD8 rs6509365 was found to be significantly more common in healthy volunteers than in SMM patients suggesting a protection effect of this variant towards melanoma development. Accordingly, CARD8 expression was found to be reduced in nevus compared to melanoma biopsies. Upon stratification, NLRP1 rs11651270 and CARD8 rs2043211 were found associated with nodular melanoma; IL1B rs1143643 to a lower value of Breslow index; IL18 rs5744256 to melanoma development in sun sensitive individuals. As expected, IL1B expression was up-regulated in tumour biopsies especially in metastatic samples, whereas IL18 was down-regulated compared to nevus. Our results demonstrated for the first time the contribution of inflammasome genes CARD8, IL1B and IL18 in SMM.
  • article 5 Citação(ões) na Scopus
    Evidence of Noncompetent HIV after Ex Vivo Purging Among ART-Suppressed Individuals
    (2017) SAMER, Sadia; NAMIYAMA, Gislene; OSHIRO, Telma; ARIF, Muhammad Shoaib; SILVA, Wanessa Cardoso da; SUCUPIRA, Maria Cecilia Araripe; JANINI, Luiz Mario; DIAZ, Ricardo Sobhie
  • article 1 Citação(ões) na Scopus
    Data on inflammasome gene polymorphisms of patients with sporadic malignant melanoma in a Brazilian cohort
    (2017) SILVA, Wanessa Cardoso da; OSHIRO, Telma M.; SA, Daniel Coelho de; FRANCO, Dilcilea D. G. S.; NETO, Cyro Festa; PONTILLO, Alessandra
    This article presents data related to our another article entitled, Genotyping and differential expression analysis of inflammasome genes in sporadic malignant melanoma reveal novel contribution of CARD8, IL1B and IL18 in melanoma susceptibility and progression (W.C. Silva, T.M. Oshiro, D.C. Sd, D.D.G.S. Franco, C. Festa Neto, A. Pontillo, 2016) In Data presented here refers to the distribution of selected inflammasome SNPs in a Brazilian case/control cohort. We have identified 4 inflammasome related Single Nucleotide Polymorphisms (SNPs) for CARDS (rs6509365); 1L1B (rs1143643) and IL18 (rs5744256 and rs1834481) related to melanoma susceptibility/protection. This data can serve as a potential prognostic marker in sporadic malignant melanoma. (C) 2017 The Authors.
  • article 1 Citação(ões) na Scopus
    Autologous and allogenic systems of HIV expansion: what is the better choice for clinical application in therapeutic vaccine?
    (2013) SILVA, Lais Teodoro da; PONTILLO, Alessandra; SILVA, Wanessa Cardoso da; ALMEIDA, Alexandre de; DUARTE, Alberto Jose da Silva; OSHIRO, Telma Miyuki
    Aims: HIV-1 expanded in an allogenic system (Al-HIV) represents a cheaper and faster alternative to the autologous virus (Au-HIV) as an antigen in anti-HIV immunotherapy. In this study, chemically inactivated HIV-1 obtained through autologous or allogenic systems were compared. Patients & methods: Au-HIV and Al-HIV obtained from cultures of peripheral blood mononuclear cells from 11 HIV+ individuals were tested for virus production, yield and time of culture, and their ability to elicit a specific immune response in vitro. Results: The allogenic system was more efficient than the autologous system. Dendritic cells pulsed with Au-HIV and Al-HIV presented a similar phenotypic profile, but only Al-HIV induced a significant increase in IFN-(+) lymphocytes. Conclusion: The use of an allogenic system displays several advantages in terms of cell manipulation, time and cost of culture, and immunogenicity.