Abstracts (complete list) - Wissenschaft Online

Viktor Kölzer, David Anz, Michaela Golic, Cornelia Wurzenberger, Stefan Endres,
Carole Bourquin
CpG Oligonucleotide Treatment Alters the Morphological
Distribution and Phenotype of Regulatory T Cells
Regulatory T cells (Treg) contribute to the maintenance of immunological homeostasis
and limit autoimmune reactions. However, Treg also suppress anti-tumor immunity and
may reduce the efficacy of cancer immunotherapy. Synthetic oligonucleotides containing
immunostimulatory CpG motifs (CpG) that signal via Toll-like receptor 9 evoke Th1-type
responses and pro-inflammatory cytokine production. They effectively induce anti-tumor
immune responses in many experimental cancer models and are currently tested in
phase III clinical studies. Despite this promising application in cancer therapy, little is
known about their influence on Treg in vivo.
In healthy, CpG-treated mice, we evaluated Foxp3-positive Treg populations in
secondary lymphoid organs by flow cytometry and immunohistology. The influence of
CpG-based cancer therapy on Treg was investigated in mice carrying subcutaneous
tumors derived from a C26 colon carcinoma.
We show that CpG treatment leads to a shift in the CD25low/CD25high Treg ratio in the
spleen and lymph nodes, with an increase of CD25low expressing Treg phenotypes. Our
analysis also demonstrates that regulatory T cells accumulate in the spleen during CpG
treatment and display an altered morphological distribution. At the same time, CpG
treatment decreases the fraction of CD25low-expressing Treg within PBMC and reduces
the accumulation of Treg in peripheral blood of tumor-bearing mice. CpG application
also slightly reduces the Treg population within tumor-draining lymph nodes.
In summary, we show that CpG-based immunotherapy leads to a shift in the balance
between CD25low and CD25high Treg phenotypes and to their accumulation in the
spleen. We suggest that the described enhancement of anti-tumor immunity through
CpG is unlikely to result from a general reduction of the Treg population. Instead, a
redistribution of Treg during immunotherapy could support anti-tumor immune
responses. Further investigation of the influence of immunotherapy on Treg may
support the development of improved therapeutic regimens.