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dc.contributor.author
Canale, Fernando Pablo
dc.contributor.author
Ramello, María Cecilia
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Nuñez, Nicolás
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Araujo Furlan, Cintia Liliana
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Bossio, Sabrina Noemí
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Gorosito Serran, Melisa
dc.contributor.author
Tosello Boari, Jimena
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del Castillo, Andrés
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Ledesma, Marta
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Sedlik, Christine
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Piaggio, Eliane
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Gruppi, Adriana
dc.contributor.author
Acosta Rodriguez, Eva Virginia
dc.contributor.author
Montes, Carolina Lucia
dc.date.available
2018-06-27T00:29:39Z
dc.date.issued
2018-01-24
dc.identifier.citation
Canale, Fernando Pablo; Ramello, María Cecilia; Nuñez, Nicolás; Araujo Furlan, Cintia Liliana; Bossio, Sabrina Noemí; et al.; CD39 expression defines cell exhaustion in tumor-infiltrating CD8+ T cells; American Association for Cancer Research; Cancer Research; 78; 1; 24-1-2018; 115-128
dc.identifier.issn
0008-5472
dc.identifier.uri
http://hdl.handle.net/11336/50228
dc.description.abstract
The ability of CD8+ T lymphocytes to eliminate tumors is limited by their ability to engender an immunosuppressive microenvironment. Here we describe a subset of tumor-infiltrating CD8+ T cells marked by high expression of the immunosuppressive ATP ectonucleotidase CD39. The frequency of CD39highCD8+ T cells increased with tumor growth but was absent in lymphoid organs. Tumor-infiltrating CD8+ T cells with high CD39 expression exhibited features of exhaustion, such as reduced production of TNF and IL2 and expression of coinhibitory receptors. Exhausted CD39+CD8+ T cells from mice hydrolyzed extracellular ATP, confirming that CD39 is enzymatically active. Furthermore, exhausted CD39+CD8+ T cells inhibited IFNg production by responderCD8+ T cells. In specimens from breast cancer and melanoma patients, CD39+CD8+ T cells were present within tumors and invaded or metastatic lymph nodes, but were barely detectable within noninvaded lymph nodes and absent in peripheral blood. These cells exhibited an exhausted phenotype with impaired production of IFNg, TNF, IL2, and high expression of coinhibitory receptors. Although T-cell receptor engagement was sufficient to induceCD39 on human CD8+ T cells, exposure to IL6 and IL27 promoted CD39 expression on stimulated CD8+ T cells from human or murine sources. Our findings show how the tumor microenvironment drives the acquisition of CD39 as an immune regulatory molecule onCD8+ T cells, withimplications for defining abiomarker of T-cell dysfunction and a target for immunotherapeutic intervention. Significance: The tumor microenvironment elicits a subset of functionally exhausted CD8+ T cells by creating conditions that induce cell surface expression of CD39, an immunosuppressive molecule that can be therapeutically targeted to restore effector T-cell function.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Association for Cancer Research
dc.rights
info:eu-repo/semantics/embargoedAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Cd39
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Cd8 T Cell
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Exhaustion
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Cancer
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Immunoregulation
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Inmunología
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
CD39 expression defines cell exhaustion in tumor-infiltrating CD8+ T cells
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2018-06-11T12:58:43Z
dc.identifier.eissn
1538-7445
dc.journal.volume
78
dc.journal.number
1
dc.journal.pagination
115-128
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Filadelfia
dc.description.fil
Fil: Canale, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Nuñez, Nicolás. Institute Curie. U-932 Immunity And Cancer; Francia
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Fil: Araujo Furlan, Cintia Liliana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Bossio, Sabrina Noemí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Gorosito Serran, Melisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: del Castillo, Andrés. Hospital Rawson; Argentina
dc.description.fil
Fil: Ledesma, Marta. Hospital Rawson; Argentina
dc.description.fil
Fil: Sedlik, Christine. Institute Curie. U-932 Immunity And Cancer; Francia
dc.description.fil
Fil: Piaggio, Eliane. Institute Curie. U-932 Immunity And Cancer; Francia
dc.description.fil
Fil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.description.fil
Fil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina
dc.journal.title
Cancer Research
dc.rights.embargoDate
2018-08-01
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/lookup/doi/10.1158/0008-5472.CAN-16-2684
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1158/0008-5472.CAN-16-2684
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info:eu-repo/semantics/altIdentifier/url/http://cancerres.aacrjournals.org/content/78/1/115
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info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/29066514