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dc.contributor.author
Lardone, Ricardo Dante
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dc.contributor.author
Chan, Alfred A.
dc.contributor.author
Lee, Agnes F.
dc.contributor.author
Foshag, Leland J.
dc.contributor.author
Faries, Mark B.
dc.contributor.author
Sieling, Peter A.
dc.contributor.author
Lee, Delphine J.
dc.date.available
2018-08-29T17:11:41Z
dc.date.issued
2017-08
dc.identifier.citation
Lardone, 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.identifier.uri
http://hdl.handle.net/11336/57514
dc.description.abstract
Intralesional 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.format
application/pdf
dc.language.iso
eng
dc.publisher
Frontiers Media S.A.
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Antitumor Immunity Mechanisms
dc.subject
Cutaneous Metastatic Melanoma
dc.subject
Intralesional Bacillus Calmette&Ndash;GuÉRin
dc.subject
Melanoma Microenvironment
dc.subject
T Cell Response
dc.subject.classification
Inmunología
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dc.subject.classification
Medicina Básica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-08-27T18:57:32Z
dc.identifier.eissn
1664-3224
dc.journal.volume
8
dc.journal.pais
Suiza
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dc.journal.ciudad
Laussane
dc.description.fil
Fil: 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.description.fil
Fil: Chan, Alfred A.. The John Wayne Cancer Institute; Estados Unidos. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos
dc.description.fil
Fil: Lee, Agnes F.. The John Wayne Cancer Institute; Estados Unidos
dc.description.fil
Fil: Foshag, Leland J.. The John Wayne Cancer Institute; Estados Unidos
dc.description.fil
Fil: Faries, Mark B.. The John Wayne Cancer Institute; Estados Unidos
dc.description.fil
Fil: Sieling, Peter A.. The John Wayne Cancer Institute; Estados Unidos
dc.description.fil
Fil: Lee, Delphine J.. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos. The John Wayne Cancer Institute; Estados Unidos
dc.journal.title
Frontiers in Immunology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fimmu.2017.00965/abstract
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3389/fimmu.2017.00965
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