Induction of antigen-specific TH 9 immunity accompanied by mast cell activation blocks tumor cell engraftment.
Int J Cancer
; 139(4): 841-53, 2016 08 15.
Article
en En
| MEDLINE
| ID: mdl-27037842
ABSTRACT
The engraftment of circulating cancer cells at distal sites represents a key step in the metastatic cascade, yet remains an unexplored target for therapeutic intervention. In this study, we establish that a vaccination strategy yielding an antigen-specific TH 9 response induces long term host surveillance and prevents the engraftment of circulating cancer cells. Specifically, we show that vaccination with a recombinant CEA IgV-like N domain, formulated with the TLR3 ligand poly IC, elicits a CEA-specific TH 9 response, wherein IL-9 secreting TH cells act in concert with CEA N domain-specific antibodies as well as activated mast cells in preventing tumor cell engraftment. The development of this immune response was dependent on TLR3, since interference with the TLR3-dsRNA complex formation led to a reduction in vaccine-imparted protection and a shift in the resulting immune response toward a TH 2 response. These findings point to the existence of an alternate tumor targeting immune mechanism that can be exploited for the purpose of developing vaccine therapies targeting tumor dissemination and engraftment.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Subgrupos de Linfocitos T
/
Especificidad del Receptor de Antígeno de Linfocitos T
/
Mastocitos
/
Antígenos de Neoplasias
/
Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Cancer
Año:
2016
Tipo del documento:
Article
País de afiliación:
Canadá