Significant reduction of human monocyte chemotactic response to monocyte-chemotactic protein 1 in patients with primary and metastatic malignant melanoma.

The recruitment of leukocytes from the peripheral blood is a key event for the development and composition of the inflammatory infiltrate in solid tumors and tumor metastases like malignant melanoma. Tumor-infiltrating lymphocytes (TIL) and tumor-associated macrophages (TAM) are thought to play a crucial rôle in tumor immunosurveillance. In malignant melanoma expression and secretion of monocyte-chemotactic protein 1 (MCP-1) have been demonstrated. MCP-1 serves as an attractant for monocytes and activated T-cells. In this study we addressed the question whether circulating monocytes show altered chemotaxis to MCP-1. Therefore the chemotactic responsiveness of monocytes towards MCP-1 was investigated in patients with primary and metastatic melanoma and compared to patients with basal cell carcinoma and healthy persons. The results show that monocytes from melanoma patients showed a significantly decreased chemotactic migration towards MCP-1 while chemotaxis to the stimulus N-formyl-methionyl-leucyl-phenylalanine (FMLP) remained normal. Patients with basal cell carcinoma showed normal monocyte chemotaxis to all stimuli tested. In primary melanoma, there was no relation of the number of TAM or TIL to the decreased chemotaxis of circulating monocytes to MCP-1. From these data it can be concluded that circulating monocytes from patients with primary and metastatic melanoma show a MCP-1-specific decrease in chemotactic migration. This may be due to deactivation or modulation of the MCP-1-receptor expression on these cells.