Strong expression of the lymphoattractant C-X-C chemokine Mig is associated with heavy infiltration of T cells in human malignant melanoma

Human malignant melanoma (MM) is a highly aggressive tumour which is partic ularly prone to specific local immune responses. To determine the microanat omical location and the species of chemokines possibly involved in the intr icate control of cell migration and positioning of immune effector cells in primary and metastatic MM lesions, the expression of those chemokines with lymphocyte and/or macrophage chemoattractant properties was analysed by in situ hybridization, GRO alpha (growth-related oncogene) and IL-8 (interleu kin 8) were expressed at ion. levels by single melanoma cells, adjacent ker atinocytes, and infiltrating leukocytes, In contrast, the lymphocyte-specif ic chemokine Mig (monokine induced by interferon-gamma) was strongly expres sed by mononuclear cells (mainly macrophages) infiltrating the tumour margi n in primary MM lesions, whereas expression was less intense in MM metastas is. IP-10 (interferon-gamma inducible protein 10) was expressed in the same loci at lower intensity. Marked infiltration of T cells was exclusively de tected in those areas which exhibited strong Mig expression, whereas areas in the vicinity of tumour cells devoid of Mig expression were not infiltrat ed. In contrast to Mig, expression of MCP-1 (macrophage chemotactic protein -1) was weaker and mainly detected in lesional basal keratinocytes, occasio nally at sites of macrophage infiltration, as well as in single melanoma ce lls. MIP-1 alpha (macrophage inflammatory protein la) showed similar, albei t weaker expression compared with MCP-1, Other chemokines relevant for the recruitment of monocytes and lymphocytes, such as RANTES (regulated on acti vation, normal T cells expressed and secreted) and MIP-1 beta were barely d etectable. In summary, the chemokine expression profiles support the notion that particularly in heavily infiltrated primary MM lesions, Mig and to a lesser extent IP-10 are important mediators of an IFN-gamma-dependent pathw ay. Due to their lymphoattractant properties and the known inhibitory effec ts on the tumour vasculature, both chemokines may be critical for the contr ol of local melanoma tumour growth. Copyright (C) 1999 John Wiley & Sons, L td.