Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function

Autores
Lardone, Ricardo Dante; Chan, Alfred A.; Lee, Agnes F.; Foshag, Leland J.; Faries, Mark B.; Sieling, Peter A.; Lee, Delphine J.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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.
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
Fil: Chan, Alfred A.. The John Wayne Cancer Institute; Estados Unidos. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos
Fil: Lee, Agnes F.. The John Wayne Cancer Institute; Estados Unidos
Fil: Foshag, Leland J.. The John Wayne Cancer Institute; Estados Unidos
Fil: Faries, Mark B.. The John Wayne Cancer Institute; Estados Unidos
Fil: Sieling, Peter A.. The John Wayne Cancer Institute; Estados Unidos
Fil: Lee, Delphine J.. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos. The John Wayne Cancer Institute; Estados Unidos
Materia
ANTITUMOR IMMUNITY MECHANISMS
CUTANEOUS METASTATIC MELANOMA
INTRALESIONAL BACILLUS CALMETTE&ndash;GU&Eacute;RIN
MELANOMA MICROENVIRONMENT
T CELL RESPONSE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/57514
Acceder
id CONICETDig_1d179847662edd4903b3cf1c01049193
oai_identifier_str oai:ri.conicet.gov.ar:11336/57514
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage FunctionLardone, Ricardo DanteChan, Alfred A.Lee, Agnes F.Foshag, Leland J.Faries, Mark B.Sieling, Peter A.Lee, Delphine J.ANTITUMOR IMMUNITY MECHANISMSCUTANEOUS METASTATIC MELANOMAINTRALESIONAL BACILLUS CALMETTE&ndash;GU&Eacute;RINMELANOMA MICROENVIRONMENTT CELL RESPONSEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Intralesional 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.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; ArgentinaFil: Chan, Alfred A.. The John Wayne Cancer Institute; Estados Unidos. Los Angeles Biomedical Research Institute At Harborucla; Estados UnidosFil: Lee, Agnes F.. The John Wayne Cancer Institute; Estados UnidosFil: Foshag, Leland J.. The John Wayne Cancer Institute; Estados UnidosFil: Faries, Mark B.. The John Wayne Cancer Institute; Estados UnidosFil: Sieling, Peter A.. The John Wayne Cancer Institute; Estados UnidosFil: Lee, Delphine J.. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos. The John Wayne Cancer Institute; Estados UnidosFrontiers Media S.A.2017-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/57514Lardone, 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; 8-20171664-3224CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fimmu.2017.00965/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2017.00965info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:45:50Zoai:ri.conicet.gov.ar:11336/57514instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 10:45:51.075CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
title Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
spellingShingle Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
Lardone, Ricardo Dante
ANTITUMOR IMMUNITY MECHANISMS
CUTANEOUS METASTATIC MELANOMA
INTRALESIONAL BACILLUS CALMETTE&ndash;GU&Eacute;RIN
MELANOMA MICROENVIRONMENT
T CELL RESPONSE
title_short Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
title_full Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
title_fullStr Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
title_full_unstemmed Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
title_sort Mycobacterium bovis Bacillus Calmette–Guérin Alters melanoma microenvironment Favoring antitumor T cell responses and improving M2 Macrophage Function
dc.creator.none.fl_str_mv Lardone, Ricardo Dante
Chan, Alfred A.
Lee, Agnes F.
Foshag, Leland J.
Faries, Mark B.
Sieling, Peter A.
Lee, Delphine J.
author Lardone, Ricardo Dante
author_facet Lardone, Ricardo Dante
Chan, Alfred A.
Lee, Agnes F.
Foshag, Leland J.
Faries, Mark B.
Sieling, Peter A.
Lee, Delphine J.
author_role author
author2 Chan, Alfred A.
Lee, Agnes F.
Foshag, Leland J.
Faries, Mark B.
Sieling, Peter A.
Lee, Delphine J.
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv ANTITUMOR IMMUNITY MECHANISMS
CUTANEOUS METASTATIC MELANOMA
INTRALESIONAL BACILLUS CALMETTE&ndash;GU&Eacute;RIN
MELANOMA MICROENVIRONMENT
T CELL RESPONSE
topic ANTITUMOR IMMUNITY MECHANISMS
CUTANEOUS METASTATIC MELANOMA
INTRALESIONAL BACILLUS CALMETTE&ndash;GU&Eacute;RIN
MELANOMA MICROENVIRONMENT
T CELL RESPONSE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv 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.
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
Fil: Chan, Alfred A.. The John Wayne Cancer Institute; Estados Unidos. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos
Fil: Lee, Agnes F.. The John Wayne Cancer Institute; Estados Unidos
Fil: Foshag, Leland J.. The John Wayne Cancer Institute; Estados Unidos
Fil: Faries, Mark B.. The John Wayne Cancer Institute; Estados Unidos
Fil: Sieling, Peter A.. The John Wayne Cancer Institute; Estados Unidos
Fil: Lee, Delphine J.. Los Angeles Biomedical Research Institute At Harborucla; Estados Unidos. The John Wayne Cancer Institute; Estados Unidos
description 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.
publishDate 2017
dc.date.none.fl_str_mv 2017-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/57514
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
1664-3224
CONICET Digital
CONICET
url http://hdl.handle.net/11336/57514
identifier_str_mv 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
1664-3224
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://journal.frontiersin.org/article/10.3389/fimmu.2017.00965/abstract
info:eu-repo/semantics/altIdentifier/doi/10.3389/fimmu.2017.00965
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.001348

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