Extracellular nucleosides and nucleotides as immunomodulators.
Immunol Rev
; 280(1): 83-92, 2017 11.
Article
en En
| MEDLINE
| ID: mdl-29027229
ABSTRACT
Some anticancer agents induce immunogenic cell death that is accompanied by the emission of danger signals into the tumor microenvironment, thus attracting and activating innate immune effectors and finally inducing anticancer immunity. The release of extracellular nucleosides such as adenosine triphosphate (ATP) from the tumor in response to anticancer therapy plays a pivotal role in the attraction of antigen presenting cells and the activation of inflammasome-mediated proinflammatory cascades. In contrast, the ectonucleotidase-catalyzed phosphohydrolysis of nucleotides to nucleosides reduces the extracellular availability of nucleotides, hence limiting the recruitment and activation of antigen-presenting cells. In addition, the (over-)production of nucleosides including adenosine by ectonucleotidases located on cancer cells and regulatory T cells can induce immunosuppression, as adenosine directly inhibits the proliferation and activation of effector T cells. Here, we discuss the importance of death metabolites for immunomodulation in general, and the role of the purine nucleotide ATP and its derivative adenosine in particular. In addition, we provide an overview on therapeutic interventions that reinstate tumor immunogenicity in conditions where nucleotide-dependent immunostimulation is obstructed.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Muerte Celular
/
Linfocitos T Reguladores
/
Factores Inmunológicos
/
Inmunoterapia
/
Neoplasias
/
Nucleósidos
/
Nucleótidos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Immunol Rev
Año:
2017
Tipo del documento:
Article
País de afiliación:
Francia