Reciprocal effects of Th1 and Treg cell inducing pathogen-associated immunomodulatory molecules on anti-tumor immunity |
| |
Authors: | Joanne Lysaght Andrew G Jarnicki Kingston H G Mills |
| |
Institution: | (1) Immune Regulation Research Group, School of Biochemistry and Immunology, Trinity College, Dublin, Ireland |
| |
Abstract: | We have addressed the hypothesis that pathogen-associated immunomodulatory molecules may influence anti-tumor immunity through
their pro- and anti-inflammatory activities and abilities to induce effector and regulatory T (Treg) cells. We found that
CpG oligonucleotides (CpG) and cholera toxin (CT), which promote Th1 or Th2/Treg cell biased responses, respectively, had
differential effects on tumor growth. Therapeutic peritumoral administration of CpG significantly reduced subcutaneous tumor
growth and prolonged survival, whereas CT enhanced tumor growth and reduced survival. Peritumoral administration of CpG enhanced
the frequency of IFN-γ-secreting and reduced IL-10-secreting CD4+ and CD8+ T cells, in the tumor and in the draining lymph nodes, whereas, CT significantly enhanced the frequency of CD4+CD25+Foxp3+ Treg cells, but reduced IFN-γ-secreting T cells infiltrating the tumor. In contrast to the beneficial effect of CpG in mice
with subcutaneous tumors, CpG or CT had no protective effect against tumor growth in the lungs when given therapeutically
by the nasal route. However, prophylactic intranasal administration of CpG significantly reduced the number of lung metastases
and this was associated with an enhanced frequency of IFN-γ-secreting CD8+ T cells in the draining lymph node and enhanced tumor-specific CTL responses. Our findings demonstrate that pathogen-associated
molecules can either inhibit or enhance anti-tumor immunity by selectively promoting the induction of effector or regulatory
T cells, and that the environment of the growing tumor influences the protective effect.
Joanne Lysaght and Andrew G. Jarnicki contributed equally. |
| |
Keywords: | Anti-tumor immunity Immunotherapeutics Th1 cell Regulatory T cell Pathogen-associated molecules |
本文献已被 PubMed SpringerLink 等数据库收录! |
|