Repositorio Institucional
Repositorio Institucional
CONICET Digital
  • Inicio
  • EXPLORAR
    • AUTORES
    • DISCIPLINAS
    • COMUNIDADES
  • Estadísticas
  • Novedades
    • Noticias
    • Boletines
  • Ayuda
    • General
    • Datos de investigación
  • Acerca de
    • CONICET Digital
    • Equipo
    • Red Federal
  • Contacto
JavaScript is disabled for your browser. Some features of this site may not work without it.
  • INFORMACIÓN GENERAL
  • RESUMEN
  • ESTADISTICAS
 
Artículo

CD39 delineates cell exhaustion in human and mouse tumor-infiltrating CD8+ T cells

Canale, Fernando PabloIcon ; Ramello, María CeciliaIcon ; Núñez, NicolásIcon ; Araujo Furlan, Cintia LilianaIcon ; Bossio, Sabrina NoemíIcon ; Gorosito Serran, MelisaIcon ; Tosello Boari, JimenaIcon ; Del Castillo, Andrés; Ledesma, Marta; Sedlik, Christine; Piaggio, Elianne; Gruppi, AdrianaIcon ; Acosta Rodriguez, Eva VirginiaIcon ; Montes, Carolina LuciaIcon
Fecha de publicación: 10/2017
Editorial: American Association for Cancer Research
Revista: Cancer Research
ISSN: 0008-5472
e-ISSN: 1538-7445
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Otras Ciencias Biológicas

Resumen

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.
Palabras clave: Thyroid Hormone Recebtor Β , Immunotherapy , Dendritic Cells , Tumor
Ver el registro completo
 
Archivos asociados
Thumbnail
 
Tamaño: 2.685Mb
Formato: PDF
.
Descargar
Licencia
info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/55124
DOI: https://doi.org/10.1158/0008-5472.CAN-16-2684
URL: https://www.ncbi.nlm.nih.gov/pubmed/29066514
Colecciones
Articulos(CIBICI)
Articulos de CENTRO DE INV.EN BIOQUI.CLINICA E INMUNOLOGIA
Citación
Canale, Fernando Pablo; Ramello, María Cecilia; Núñez, Nicolás; Araujo Furlan, Cintia Liliana; Bossio, Sabrina Noemí; et al.; CD39 delineates cell exhaustion in human and mouse tumor-infiltrating CD8+ T cells; American Association for Cancer Research; Cancer Research; 78; 1; 10-2017; 115-128
Compartir
Altmétricas
 

Enviar por e-mail
Separar cada destinatario (hasta 5) con punto y coma.
  • Facebook
  • X Conicet Digital
  • Instagram
  • YouTube
  • Sound Cloud
  • LinkedIn

Los contenidos del CONICET están licenciados bajo Creative Commons Reconocimiento 2.5 Argentina License

https://www.conicet.gov.ar/ - CONICET

Inicio

Explorar

  • Autores
  • Disciplinas
  • Comunidades

Estadísticas

Novedades

  • Noticias
  • Boletines

Ayuda

Acerca de

  • CONICET Digital
  • Equipo
  • Red Federal

Contacto

Godoy Cruz 2290 (C1425FQB) CABA – República Argentina – Tel: +5411 4899-5400 repositorio@conicet.gov.ar
TÉRMINOS Y CONDICIONES