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 metastasis and strong malignant potential. The local immune response against melanoma is compromised by multiple escape mechanisms of the tumor, which have been uncovered partially by thorough molecular and immunological analyses. These analyses were completed recently by gene-expression profiling. In this article, we summarize data suggesting that melanoma-derived histamine should be included as an important factor involved in bi-directional interactions 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-receptor balance) and indirectly shifting the local T-cell polarization towards a predominance of T helper 2 cells. The effect of endogenously produced histamine on the regulation of growth of melanoma cells depends whether H1 or H2 receptors are involved preferentially; furthermore, a shift towards local Th2 dominance of the surrounding cytokines, mediated by histamine, is observed.