Dendritic cells: integrative elements of the immune system - an applied approach

• Grant number: 09/54599-5
• Support Opportunities: Research Projects - Thematic Grants
• Start date: June 01, 2010
• End date: May 31, 2015
• Field of knowledge: Biological Sciences - Immunology - Cellular Immunology
• Principal Investigator: Jose Alexandre Marzagão Barbuto
• Grantee: Jose Alexandre Marzagão Barbuto
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 12/17643-9 - DENDRITIC CELLS FUNCTION DISABILITY PROMOTED BY CANCER MIGHT BEGIN AT THEIR HEMATOPOIETIC PRECURSORS, BP.PD; 12/13428-6 - Functional impairment of monocyte-derived dendritic cells in cancer patients: involvement of p38 and ERK (p44/p42) MAPK signaling pathway, BP.DD; 11/15371-9 - STAT3 inhibition by thymosin alpha-1: Effective strategy for the functional recovery of cancer patients" monocyte-derived dendritic cells?, BP.MS; + associated scholarships 11/08905-7 - Study of mechanisms involved in modulation of T lymphocyte response against tumor antigens by dendritic cells derived from cancer patients monocytes, BP.DR; 11/00597-1 - NF-kB functional evaluation in dendritic cells from patients with breast cancer, BP.DR; 10/18139-7 - Cellular interactions in three-dimensional environment between dendritic cell-tumor cell hybrids and human lymphocytes: in search of strategies for enhancing antitumor vaccines, BP.DD; 11/01082-5 - Analysis of the roles of membrane CD83 molecule in the biology of the immune response., BP.IC; 10/13925-4 - Functional impairment of monocyte-derived dendritic cells in cancer patients: involvement of p38MAPK signaling pathway and heat shock protein HSP27, BP.MS; 10/15312-0 - Suppressors of cytokines signaling (SOCS) in the functional modulation of dendritic cells derived from patients with cancer, BP.DR - associated scholarships

Abstract

Dendritic cells (DCs) constitute key elements that influence strongly the consequences of an encounter of the organism with any antigen. Immune response patterns, ranging from tolerance to antigen elimination or the establishment of immunopathological states depend on the way DCs interact with T lymphocytes. Our laboratory has been studying DCs and found many intriguing behaviors of these cells, mainly in cancer. The present project intends to follow up on these studies, aiming to add to our understanding of the role of human DCs role in the immune system, both in health and sickness, and of the cellular and molecular mechanisms by which DCs act in the organism. This goal will be pursued by the development of, initially, nine subprojects: two that investigate DC physiological functions, without interference of pathological conditions; three others that investigate DC behavior in stress situations, caused by cancer or its treatment; and four subprojects that aim to understand and develop strategies to interfere with DCs as therapeutic tools. For the development of the project, the laboratory will establish, standardize and use different methodologies, ranging from cell culture and differentiation to gene silencing with siRNAs, allowing an encompassing analysis of DC biological behavior and offering good training opportunities for the students involved. As a general, background, objective, the project intends to integrate the data obtained in a view, where DCs assume the role of indicators of the dynamic state of the immune system and whose analysis may, therefore, facilitate immunomodulatory approaches. (AU)

Scientific publications

(19)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CLAVIJO-SALOMON, MARIA A.; BERGAMI-SANTOS, PATRICIA C.; BARBUTO, JOSE ALEXANDRE M.. Immunomonitoring reveals interruption of anergy after vaccination in a case of type-2-papillary renal cell carcinoma. Immunotherapy, v. 9, n. 4, p. 319-329, MAR 2017. (11/05331-0, 09/54599-5, 12/23478-0)

TAMAYO, LENKA V.; GOUVEA, LIGIANE R.; SOUSA, ANNA C.; ALBUQUERQUE, RONNIEL M.; TEIXEIRA, SARAH FERNANDES; DE AZEVEDO, RICARDO ALEXANDRE; LOURO, SONIA R. W.; FERREIRA, ADILSON KLEBER; BERALDO, HELOISA. Copper(II) complexes with naringenin and hesperetin: cytotoxic activity against A 549 human lung adenocarcinoma cells and investigation on the mode of action. BIOMETALS, v. 29, n. 1, p. 39-52, FEB 2016. (13/07273-2, 09/54599-5)

TEIXEIRA, SARAH FERNANDES; DE AZEVEDO, RICARDO ALEXANDRE; SILVA, ARTHUR CARVALHO; BRAGA, RODOLPHO CAMPOS; JORGE, SALOMAO DORIA; MARZAGAO BARBUTO, JOSE ALEXANDRE; ANDRADE, CAROLINA HORTA; FERREIRA, ADILSON KLEBER. Evaluation of cytotoxic effect of the combination of a pyridinyl carboxamide derivative and oxaliplatin on NCI-H1299 human non-small cell lung carcinoma cells. BIOMEDICINE & PHARMACOTHERAPY, v. 84, p. 1019-1028, DEC 2016. (16/05351-4, 09/54599-5, 13/05396-0, 15/18528-7, 14/07341-0, 14/24455-0, 13/07273-2, 14/14267-1)

ROMAGNOLI, GRAZIELA GORETE; ZELANTE, BRUNA BARBOSA; TONIOLO, PATRICIA ARGENTA; MIGLIORI, ISABELLA KATZ; BARBUTO, JOSE ALEXANDRE M.. Dendritic cell-derived exosomes may be a tool for cancer immunotherapy by converting tumor cells into immunogenic targets. FRONTIERS IN IMMUNOLOGY, v. 5, JAN 19 2015. (04/09956-0, 09/54599-5)

MARQUES, OTAVIO CABRAL; ARSLANIAN, CHRISTINA; RAMOS, RODRIGO NALIO; MORATO, MARIANA; SCHIMKE, LENAFRIEDERIKE; SOEIRO, PAULO VITOR; JANCAR, SONIA; FERREIRA, JANIRA FERNANDES; WEBER, CRISTINA WORM; KUNTZE, GISELE; et al. Dendritic cells from X-linked hyper-IgM patients present impaired responses to Candida albicans and Paracoccidioides brasiliensis. Journal of Allergy and Clinical Immunology, v. 129, n. 3, p. 778-786, MAR 2012. (09/54599-5)

TONIOLO, PATRICIA A.; LIU, SUHU; YEH, JENNIFER E.; YE, DARWIN Q.; BARBUTO, JOSE ALEXANDRE M.; FRANK, DAVID A.. Deregulation of SOCS5 suppresses dendritic cell function in chronic lymphocytic leukemia. ONCOTARGET, v. 7, n. 29, p. 46301-46314, JUL 19 2016. (10/15312-0, 12/01623-9, 09/54599-5)

MACHADO, FABRICIO C.; GIROLA, NATALIA; MAIA, VERA S. C.; BERGAMI-SANTOS, PATRICIA C.; MORAIS, ALICE S.; AZEVEDO, RICARDO A.; FIGUEIREDO, CARLOS R.; BARBUTO, JOSE A. M.; TRAVASSOS, LUIZ R.. Immunomodulatory Protective Effects of Rb9 Cyclic-Peptide in a Metastatic Melanoma Setting and the Involvement of Dendritic Cells. FRONTIERS IN IMMUNOLOGY, v. 10, JAN 15 2020. (10/51423-0, 09/54599-5)

PINHO, MARIANA PEREIRA; SUNDARASETTY, BALA SAI; BERGAMI-SANTOS, PATRICIA CRUZ; STEPONAVICIUS-CRUZ, KAREN; FERREIRA, ADILSON KLEBER; STRIPECKE, RENATA; BARBUTO, JOSE ALEXANDRE M.. Dendritic-tumor cell hybrids induce tumor-specific immune responses more effectively than the simple mixture of dendritic and tumor cells. CYTOTHERAPY, v. 18, n. 4, p. 570-580, APR 2016. (13/26044-4, 09/54599-5, 12/10939-0)

FERREIRA, ADILSON KLEBER; MESQUITA PASQUALOTO, KERLY FERNANDA; KRUYT, FRANK A. E.; PALACE-BERL, FANNY; AZEVEDO, RICARDO ALEXANDRE; TURRA, KELY MEDEIROS; RODRIGUES, CECILIA PESSOA; FRANCO FERREIRA, ANA CAROLINA; CLAVIJO SALOMON, MARIA ALEJANDRA; DE SA JUNIOR, PAULO LUIZ; et al. BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity. Toxicology and Applied Pharmacology, v. 295, p. 56-67, MAR 15 2016. (09/54599-5, 13/05396-0, 14/07341-0, 13/07273-2, 14/14267-1)

CLAVIJO-SALOMON, MARIA A.; SALCEDO, ROSALBA; ROY, SOUMEN; DAS NEVES, RODRIGO X.; DZUTSEV, AMIRAN; SALES-CAMPOS, HELIOSWILTON; BORBELY, KAREN STEPONAVICIUS-CRUZ; SILLA, LUCIA; ORANGE, JORDAN S.; MACE, EMILY M.; et al. Human NK cells prime inflammatory DC precursors to induce Tc17 differentiation. BLOOD ADVANCES, v. 4, n. 16, p. 3990-4006, AUG 25 2020. (17/13686-9, 14/10290-9, 09/54599-5, 11/05331-0, 12/23478-0)

STEPONAVICIUS-CRUZ, KAREN; FREITAS, VANESSA MORAIS; BARBUTO, JOSE ALEXANDRE M.; BARTOLO, P; FERNANDES, P. Dendritic cells and T lymphocytes interactions in a novel 3D system. X INTERNATIONAL CONFERENCE ON STRUCTURAL DYNAMICS (EURODYN 2017), v. 59, p. 8-pg., 2013-01-01. (10/18139-7, 09/54599-5)

RAMOS, RODRIGO NALIO; DE MORAES, CRISTIANO JACOB; ZELANTE, BRUNA; BARBUTO, JOSE ALEXANDRE M.. What Are the Molecules Involved in Regulatory T-Cells Induction by Dendritic Cells in Cancer?. CLINICAL & DEVELOPMENTAL IMMUNOLOGY, 2013. (11/08905-7, 09/54599-5)

RAMOS, RODRIGO NALIO; CHIN, LILIAN SALLY; DOS SANTOS, ANA PAULA S. A.; BERGAMI-SANTOS, PATRICIA CRUZ; LAGINHA, FABIO; BARBUTO, JOSE ALEXANDRE M.. Monocyte-derived dendritic cells from breast cancer patients are biased to induce CD4(+)CD25(+)Foxp3(+) regulatory T cells. Journal of Leukocyte Biology, v. 92, n. 3, p. 673-682, SEP 2012. (09/54599-5, 09/02074-6)

PINHO, MARIANA PEREIRA; MIGLIORI, ISABELLA KATZ; FLATOW, ELIZABETH ALEXANDRA; BARBUTO, JOSE ALEXANDRE M.. Dendritic cell membrane CD83 enhances immune responses by boosting intracellular calcium release in T lymphocytes. Journal of Leukocyte Biology, v. 95, n. 5, p. 755-762, MAY 2014. (11/01082-5, 09/54599-5)

TEIXEIRA, SARAH FERNANDES; DE AZEVEDO, RICARDO ALEXANDRE; CLAVIJO SALOMON, MARIA ALEJANDRA; JORGE, SALOMAO DORIA; LEVY, DEBORA; BYDLOWSKI, SERGIO PAULO; RODRIGUES, CECILIA PESSOA; PIZZO, CELIA REGINA; MARZAGAO BARBUTO, JOSE ALEXANDRE; FERREIRA, ADILSON KLEBER. Synergistic anti-tumor effects of the combination of a benzofuroxan derivate and sorafenib on NCI-H460 human large cell lung carcinoma cells. BIOMEDICINE & PHARMACOTHERAPY, v. 68, n. 8, p. 1015-1022, OCT 2014. (13/07273-2, 09/54599-5)

PORCHIA, BRUNA F. M. M.; MORENO, ANA CAROLINA R.; RAMOS, RODRIGO N.; DINIZ, MARIANA O.; DE ANDRADE, LAIS HELENA T. M.; ROSA, DANIELA S.; BARBUTO, JOSE ALEXANDRE M.; BOSCARDIN, SILVIA B.; FERREIRA, LUIS CARLOS S.. Herpes Simplex Virus Glycoprotein D Targets a Specific Dendritic Cell Subset and Improves the Performance of Vaccines to Human Papillomavirus-Associated Tumors. MOLECULAR CANCER THERAPEUTICS, v. 16, n. 9, p. 1922-1933, SEP 1 2017. (09/54599-5, 16/00708-1, 11/20917-0, 15/16505-0, 11/08905-7, 11/51218-0, 14/15061-8)

CLAVIJO-SALOMON, MARIA A.; RAMOS, RODRIGO N.; CRIPPA, ALEXANDRE; PIZZO, CELIA R.; BERGAMI-SANTOS, PATRICIA C.; BARBUTO, JOSE ALEXANDRE M.. Monocyte-derived dendritic cells reflect the immune functional status of a chromophobe renal cell carcinoma patient: Could it be a general phenomenon?. CANCER IMMUNOLOGY IMMUNOTHERAPY, v. 64, n. 2, p. 161-171, FEB 2015. (11/05331-0, 09/54599-5, 12/23478-0)

TONIOLO, PATRICIA A.; LIU, SUHU; YEH, JENNIFER E.; MORAES-VIEIRA, PEDRO M.; WALKER, SARAH R.; VAFAIZADEH, VIDA; BARBUTO, JOSE ALEXANDRE M.; FRANK, DAVID A.. Inhibiting STAT5 by the BET Bromodomain Inhibitor JQ1 Disrupts Human Dendritic Cell Maturation. JOURNAL OF IMMUNOLOGY, v. 194, n. 7, p. 3180-3190, APR 1 2015. (12/01623-9, 09/54599-5)

RAMOS, RODRIGO NALIO; DE MORAES, CRISTIANO JACOB; ZELANTE, BRUNA; BARBUTO, JOSE ALEXANDRE M.. What Are the Molecules Involved in Regulatory T-Cells Induction by Dendritic Cells in Cancer?. CLINICAL & DEVELOPMENTAL IMMUNOLOGY, v. N/A, p. 10-pg., 2013-01-01. (09/54599-5, 11/08905-7)