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dc.creatorLardone, Ricardo Dante-
dc.creatorChan, Alfred A.-
dc.creatorLee, Agnes F.-
dc.creatorFoshag, Leland J.-
dc.creatorFaries, Mark B.-
dc.creatorSieling, Peter A.-
dc.creatorLee, Delphine J.-
dc.date2018-08-29T17:11:41Z-
dc.date2018-08-29T17:11:41Z-
dc.date2017-08-
dc.date2018-08-27T18:57:32Z-
dc.date.accessioned2019-04-29T15:46:45Z-
dc.date.available2019-04-29T15:46:45Z-
dc.date.issued2017-08-
dc.identifierLardone, Ricardo Dante; Chan, Alfred A.; Lee, Agnes F.; Foshag, Leland J.; Faries, Mark B.; et al.; Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function; Frontiers Media S.A.; Frontiers in Immunology; 8; 8-2017-
dc.identifierhttp://hdl.handle.net/11336/57514-
dc.identifier1664-3224-
dc.identifierCONICET Digital-
dc.identifierCONICET-
dc.identifier.urihttp://rodna.bn.gov.ar:8080/jspui/handle/bnmm/301779-
dc.descriptionIntralesional Mycobacterium bovis bacillus Calmette–Guérin (BCG) has long been a relatively inexpensive therapy for inoperable cutaneous metastatic melanoma (CMM), although intralesional BCG skin mechanisms remain understudied. We analyzed intralesional BCG-treated CMM lesions combined with in vitro studies to further investigate BCG-altered pathways. Since macrophages play a pivotal role against both cancer and mycobacterial infections, we hypothesized BCG regulates macrophages to promote antitumor immunity. Tumor-associated macrophages (M2) infiltrate melanomas and impair antitumor immunity. BCG-treated, in vitro-polarized M2 (M2-BCG) showed transcriptional changes involving inflammation, immune cell recruitment, cross talk, and activation pathways. Mechanistic network analysis indicated M2-BCG potential to improve interferon gamma (IFN-γ) responses. Accordingly, frequency of IFN-γ-producing CD4+ T cells responding to M2-BCG vs. mock-treated M2 increased (p < 0.05). Moreover, conditioned media from M2-BCG vs. M2 elevated the frequency of granzyme B-producing CD8+ tumor-infiltrating lymphocytes (TILs) facing autologous melanoma cell lines (p < 0.01). Furthermore, transcriptome analysis of intralesional BCG-injected CMM relative to uninjected lesions showed immune function prevalence, with the most enriched pathways representing T cell activation mechanisms. In vitro-infected MM-derived cell lines stimulated higher frequency of IFN-γ-producing TIL from the same melanoma (p < 0.05). Our data suggest BCG favors antitumor responses in CMM through direct/indirect effects on tumor microenvironment cell types including macrophages, T cells, and tumor itself.-
dc.descriptionFil: Lardone, Ricardo Dante. The John Wayne Cancer Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Química Biológica de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Centro de Investigaciones en Química Biológica de Córdoba; Argentina-
dc.descriptionFil: Chan, Alfred A.. The John Wayne Cancer Institute; Estados Unidos. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos-
dc.descriptionFil: Lee, Agnes F.. The John Wayne Cancer Institute; Estados Unidos-
dc.descriptionFil: Foshag, Leland J.. The John Wayne Cancer Institute; Estados Unidos-
dc.descriptionFil: Faries, Mark B.. The John Wayne Cancer Institute; Estados Unidos-
dc.descriptionFil: Sieling, Peter A.. The John Wayne Cancer Institute; Estados Unidos-
dc.descriptionFil: Lee, Delphine J.. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos. The John Wayne Cancer Institute; Estados Unidos-
dc.formatapplication/pdf-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherFrontiers Media S.A.-
dc.relationinfo:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fimmu.2017.00965/abstract-
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fimmu.2017.00965-
dc.rightsinfo:eu-repo/semantics/openAccess-
dc.rightshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/-
dc.sourcereponame:CONICET Digital (CONICET)-
dc.sourceinstname:Consejo Nacional de Investigaciones Científicas y Técnicas-
dc.sourceinstacron:CONICET-
dc.subjectANTITUMOR IMMUNITY MECHANISMS-
dc.subjectCUTANEOUS METASTATIC MELANOMA-
dc.subjectINTRALESIONAL BACILLUS CALMETTE&ndash;GU&Eacute;RIN-
dc.subjectMELANOMA MICROENVIRONMENT-
dc.subjectT CELL RESPONSE-
dc.subjectInmunología-
dc.subjectMedicina Básica-
dc.subjectCIENCIAS MÉDICAS Y DE LA SALUD-
dc.titleMycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function-
dc.typeinfo:eu-repo/semantics/article-
dc.typeinfo:eu-repo/semantics/publishedVersion-
dc.typeinfo:ar-repo/semantics/articulo-
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