Induction of Antigen-Specific TH9 Immunity Accompanied by Mast Cell Activation Blocks Tumor Cell Engraftment

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 the present study, we establish that a vaccination strategy yielding antigen-specific T_H9 responses 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 I:C, elicits CEA-specific T_H9 responses, wherein IL-9 secreting T_H 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 towards a T_H2 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. This article is protected by copyright. All rights reserved.

from Cancer via ola Kala on Inoreader http://ift.tt/235hPxc
via IFTTT