Abstracts (complete list) - Wissenschaft Online

Anita Correll, Andrea Tuettenberg, Christian Becker, Jürgen Knop, Helmut Jonuleit
Stage-dependent quantification of regulatory T cells and
antigen-specific T cell responses in melanoma patients
Naturally occurring CD4 + CD25 + regulatory T cells (nTregs) are key players in the
tolerance network. As immunosuppression seems to be one important way by which
tumors succeed in immune escape, nTregs are assumed to play a crucial role in
mechanisms contributing to the development and progression of cancer.
Unlike the murine system, human nTregs cannot be distinguished from conventional T
helper cells easily by markers like CD25 or Foxp3 since both are also expressed by CD4
+ T helper cells upon activation. In this study, we used different marker combinations
for nTreg phenotyping (CD4, CD25, CD127, Foxp3, HLA-DR) for quantitative analysis of
human nTregs in the peripheral blood of stage II-IV melanoma patients. Using this
experimental setting, we observed increased ratios of CD4 + CD25 + Foxp3 + HLA-DR
+ CD127 low Tregs in peripheral blood of melanoma patients compared to healthy
volunteers. Moreover, the relative ratios of nTregs increased with the progression of
disease. Additionally, accumulation of nTregs in progressed melanoma patients also
correlated with a general reduction of T cell responsiveness not only to different tumorassociated
antigens but also to various recall antigens. These observations, the
suppressed T cell reactivity in combination with increased nTreg ratios in patients with
progressive melanoma possibly explain the disappointing success of immunotherapies in
the patients.