Paracrine and autocrine interactions in melanoma: histamine is a relevant player in local regulation

Malignant melanoma is a life-threatening tumor, with a high rate of metasta sis and strong malignant potential. The local immune response against melan oma is compromised by multiple escape mechanisms of the tumor, which have b een uncovered partially by thorough molecular and immunological analyses. T hese analyses were completed recently by gene-expression profiling. In this article, we summarize data suggesting that melanoma-derived histamine shou ld be included as an important factor involved in bi-directional interactio ns between the tumor tissue and infiltrating immune cells. The presence and activity of histamine seems to be relevant by both directly stimulating or suppressing growth of the melanoma (depending on the local histamine-recep tor balance) and indirectly shifting the local T-cell polarization towards a predominance of T helper 2 cells.