Immune modulation by melanoma-derived factors

Melanomas, while the less common of skin cancers, are highly aggressive and once they metastasize usually indicate a poor prognosis. Melanomas are in many cases immunogenic and thus have been a prime target for immunotherapy, which has resulted in objective responses in some patients. To understand why antitumor immunity fails, and for the purpose of discovering new targets to improve therapy, there has been great interest to analyse the antitumor immune responses which exist in these patients, and uncover mechanisms which block tumor-specific immune responses. It is now evident that immunosuppressive cell networks and factors play a major role in the failure of the antitumor immune responses and therapies to eradicate the tumor. In this review, the factors produced by melanomas which can modulate and enhance these suppressive mechanisms are discussed. The roles of immature dendritic cells, neutrophils, T-regulatory cells, myeloid-derived suppressor cells and M2 macrophages or tumor-associated macrophages are described. Furthermore, taking into consideration of the cross-talk which exists among these different cell types and the cycle of immunosuppression which is evident in melanoma cancer patients and animal models, will be important for future therapeutic approaches.