1. ¹Department of Genetics, Cell and Immunobiology, Semmelweis University, Budapest, Hungary
2. ²First Department of Obstetrics and Gynecology, Semmelweis University, Budapest, Hungary
3. ³Hungarian Academy of Sciences, Immunogenomics Research Group, Budapest, Hungary

Correspondence: Dr Andras Falus, Department of Genetics, Cell and Immunobiology, Semmelweis University, H-1089. Budapest, Nagyvarad ter 4, Hungary. E-mail: faland@dgci.sote.hu

Received 29 May 2006; Revised 27 August 2006; Accepted 13 September 2006; Published online 9 November 2006.

Abstract

Many studies detect elevated numbers of mast cells in tumors, but it is still controversial whether they are beneficial or detrimental for tumor cells. Furthermore, many tumors, such as melanomas, produce large quantities of transforming growth factor (TGF)- and during tumorigenesis the apoptotic and growth-inhibitory effects of TGF-s are lost. Based on these data we investigated the gene expression changes in TGF-I-treated human mast cells with DNA microarray and detected 45 differentially regulated genes, among them T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3). As the major sources of TIM-3 ligand galectin-9 are not tumor cells, but rather mast cells, this raises the possibility of an autocrine mechanism resulting in local immunosuppression through the elevated TIM-3 expression by TGF-I. Interestingly, not only melanoma tissue sections contained TIM-3-positive mast cells, but we detected this protein also in melanoma cells. Furthermore, TIM-3 was expressed in both WM35 and HT168-M1 melanoma cell lines at a higher level than in isolated epidermal melanocytes, which can contribute to the lower adhering capacity of tumor cells. In conclusion, the immunoregulatory molecule TIM-3 in TGF--stimulated mast cells and melanoma cells may support the survival of this tumor type.