Expression and function of indoleamine 2,3-dioxygenase in cutaneous malignant melanoma / 实用医学杂志

ABSTRACT

Objective To investigate the expression and its potential effect on the immune function of indoleamine 2 ,3-dioxygenase (IDO) in cutaneous malignant melanoma (MM). Methods The IDO protein expression in MM tissue from 30 patients,normal skin from 10 of these patients and normal foreskin of 10 healthy subjects were observed by skin immunohistochemical staining. The number of IDO positive cells were counted. Epidermal cells of MM tissue were isolated and cultured with Hanks solution contained 100 μmol/L tryptophan. The concentration of tryptophan metabolite and kynurenine were detected in supernatant ,reflecting the ability to metabolize the tryptophan of the skin cells. Further ,the isolated epidermal cells were co-cultured with T cells. The influence on PHA-stimulated T cell proliferation were observed. Results IDO(+)cells were almost undetectable in the normal skin,but IDO(+)cells greatly accumulated in epidermis of MM tissue. The percentage of IDO(+) cells/total cells[(28.5 ± 9.4)%]was significantly higher than that of normal skin from healthy subjects[(3.4 ± 1.5)%,P<0.05]and control skin from MM patient[(4.7 ± 2.3)%,P<0.05]. Compared with the epidermal cells from the healthy skin,the IDO(+)cells from MM tissue had a stronger ability to metabolize tryptophan into kyn-urenine in vitro. These isolated IDO-competent epidermal cellscould inhibit PHA-stimulated T cell proliferation. Conclusions IDO(+)cells greatly accumulated in cutaneous MM tissue ,which might induce a local immune tolerant microenvironment.