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
em 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Subpopulações de Linfócitos T
/
Especificidade do Receptor de Antígeno de Linfócitos T
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Mastócitos
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Antígenos de Neoplasias
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Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Canadá