Chemotherapeutic Agents in Noncytotoxic Concentrations Increase Antigen Presentation by Dendritic Cells via an IL-12-Dependent Mechanism

Página do item simplificado
dc.contributor.authorShurin, Galina V.
dc.contributor.authorTourkova, Irina L.
dc.contributor.authorKaneno, Ramon [UNESP]
dc.contributor.authorShurin, Michael R.
dc.contributor.institutionUniversity of Pittsburgh
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-20T13:51:08Z
dc.date.available2014-05-20T13:51:08Z
dc.date.issued2009-07-01
dc.description.abstractAntineoplastic chemotherapeutic agents may indirectly activate dendritic cells (DCs) by inducing the release of danger signals from dying tumor cells. Whereas the direct cytotoxic or inhibitory effect of conventional chemotherapy on DCs has been reported, modulation of DC function by chemotherapeutic agents in low noncytotoxic concentrations has not yet been investigated. We have tested the effects of different classes of antineoplastic chemotherapeutic agents used in low noncytotoxic concentrations on the Ag-presenting function of DCs. We revealed that paclitaxel, doxorubicin, mitomycin C, and methotrexate up-regulated the ability of DCs to present Ags to Ag-specific T cells. Stimulation of DC function was associated with the up-regulation of expression of Ag-processing machinery components and costimulatory molecules on DCs, as well as increased IL-12p70 expression. However, the ability of DCs treated with paclitaxel, methotrexate, doxorubicin, and vinblastine to increase Ag presentation to Ag-specific T cells was abolished in DCs generated from IL-12 knockout mice, indicating that up-regulation of Ag presentation by DCs is IL-12-dependent and mediated by the autocrine or paracrine mechanisms. At the same time, IL-12 knockout and wild-type DCs demonstrated similar capacity to up-regulate OVA presentation after their pretreatment with low concentrations of mitomycin C and vincristine, suggesting that these agents do not utilize IL-12-mediated pathways in DCs for stimulating Ag presentation. These findings reveal a new mechanism of immunopotentiating activity of chemotherapeutic agents-a direct immunostimulatory effect on DCs (chemomodulation)-and thus provide a strong rationale for further assessment of low-dose chemotherapy given with DC vaccines for cancer treatment. The Journal of Immunology, 2009, 183: 137-144.en
dc.description.affiliationUniv Pittsburgh, Dept Pathol, Med Ctr, Div Expt Pathol, Pittsburgh, PA 15213 USA
dc.description.affiliationUniv Pittsburgh, Dept Immunol, Med Ctr, Pittsburgh, PA 15213 USA
dc.description.affiliationSão Paulo State Univ, Dept Microbiol & Immunol, Inst Biosci, São Paulo, Brazil
dc.description.affiliationUnespSão Paulo State Univ, Dept Microbiol & Immunol, Inst Biosci, São Paulo, Brazil
dc.description.sponsorshipNational Institutes of Health (NIH)
dc.description.sponsorshipIdNIH: RO1-CA084270
dc.format.extent137-144
dc.identifierhttp://dx.doi.org/10.4049/jimmunol.0900734
dc.identifier.citationJournal of Immunology. Bethesda: Amer Assoc Immunologists, v. 183, n. 1, p. 137-144, 2009.
dc.identifier.doi10.4049/jimmunol.0900734
dc.identifier.issn0022-1767
dc.identifier.lattes8845835550637809
dc.identifier.orcid0000-0002-4292-3298
dc.identifier.urihttp://hdl.handle.net/11449/18263
dc.identifier.wosWOS:000275119400016
dc.language.isoeng
dc.publisherAmer Assoc Immunologists
dc.relation.ispartofJournal of Immunology
dc.relation.ispartofjcr4.539
dc.relation.ispartofsjr2,837
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.titleChemotherapeutic Agents in Noncytotoxic Concentrations Increase Antigen Presentation by Dendritic Cells via an IL-12-Dependent Mechanismen
dc.typeArtigo
dcterms.licensehttp://www.jimmunol.org/site/misc/authorinstructions.xhtml#copyright
dcterms.rightsHolderAmer Assoc Immunologists
unesp.author.lattes8845835550637809[3]
unesp.author.orcid0000-0002-4292-3298[3]
unesp.author.orcid0000-0002-6570-7395[4]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt

Arquivos

Licença do Pacote
Agora exibindo 1 - 2 de 2
Nenhuma Miniatura disponível
Nome:
license.txt
Tamanho:
1.71 KB
Formato:
Item-specific license agreed upon to submission
Descrição:
Nenhuma Miniatura disponível
Nome:
license.txt
Tamanho:
1.71 KB
Formato:
Item-specific license agreed upon to submission
Descrição:

Coleções

Artigos - Microbiologia e Imunologia - IBB