Abstract Book 2010 - CIMT Annual Meeting

031 Gross | Immune monitoring
Monitoring of vaccine-specific regulatory and helper CD4+
and cytolytic CD8+ T cells after vaccination with autologous
antigen-loaded dendritic cells
Stefanie Gross, Annett Hamann, Gerold Schuler, Eckhart Kämpgen, Beatrice Schuler-Thurner
Department of Dermatology, University of Erlangen, Germany
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Cancer vaccines have been shown to induce tumorspecific
CD8+ cytolytic T cells (CTL) in the blood
of cancer patients. However, clinical outcome often
remains poor. This ‚‘cancer vaccine paradox‘‘ can
nowadays be readily explained by tumor-escape
and immune-regulatory mechanisms. It has been
suspected, that cancer vaccines of different types
might not only induce the desired CTL response
but simultaneously also expand antigen-specific
regulatory T cells (Treg), thus counteracting productive
immune responses and preventing clinical
efficacy of cancer vaccines. Of note is that it has
been claimed that mature dendritic cells (DC) are
not only expanding antigen-specific helper T cells
but also the disadvantageous Tregs. The induction
of antigen-specific Tregs by DC and other vaccines
has, however, not yet been studied systematically
by advanced immunomonitoring techniques.
Frequencies and nature of vaccine-induced CD8+
cytolytic and CD4+ helper or regulatory T cells in
vaccinated cancer patients were analyzed ex vivo
by 9 color flow cytometry. MHC Class I and MHC-
Class II multimer-staining for different tyrosinase,
MelanA, gp100, NY-ESO1 or MAGE3 epitopes was
combined with intracellular staining for different
signature-transcription factors such as FoxP3
(Treg), GATA-3 (Th2) and RoR t (Th17) for CD4+
T cells or function-associated molecules like perforine
and granzyme B for CD8+ T cells.
In contrast to common belief our data so far do
not support the notion that tumor vaccination with
autologous mature dendritic cells bears the risk
to induce immuno-suppressive regulatory T cells.
Remarkably, the same vaccine induced different
immune responses in patients (Th1, Th2, granzyme
B), pinpointing the likely benefit of patientselection
and vaccination at early disease stages.