A6: Role for neuropeptides in melanoma specific immunity vs. tolerance induction

Previous studies have shown that the tumor progression of malignant melanoma is apparently induced by a tolerogenic milieu caused by the tumor itself, which also causes the induction of regulatory T-cells that inhibit effector cells. Furthermore, by the induction of  T reg anti-inflammatory cytokines like IL-10 and TGF-ß were discussed as well as neuropeptides like CGRP, VIP and PACAP. This probably occurs through the induction of tolerogenic dendritic cells as antigen-presenting cells (reduction of co-stimulating signals like CD80 and CD86). On the other side in case of vitiligo, it could be found that T cell-mediated or antibody-mediated autoimmunity against melanocyte antigens may lead to a loss of pigment. In this project, the frequency of tumor antigen-specific effector and regulatory T cells from blood and tissue should be studied in patients with melanoma and vitiligo. Skin biopsies of patients should be investigated in terms of the composition of the inflammatory infiltrates and the expression of pro- and anti-inflammatory cytokines under particular consideration of neuropeptides. In this context pro-inflammatory and regulatory T cells should also be isolated from melanoma tissue and vitiligo biopsies i.e. by employing laser dissection and examined ex vivo with respect to the expression of pro- and anti-inflammatory cytokines and chemokines as well as neuropeptides CGRP, VIP and PACAP.

References

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Veldman, ….. and Hertl, M. (2006). Inhibition of the transcription factor Foxp3 converts desmoglein 3-specific type 1 regulatory T cells into T helper 2-like cells. J Immunol. 176:3215-3222.