Myeloid cells obtained from the blood but not from the tumor can suppress T-cell proliferation in patients with melanoma.

Abstract

Myeloid-derived suppressor cells (MDSC) have emerged as an immune-regulatory cell type that is expanded in tumor-bearing mice, but less is known about their immune-suppressive role in patients with cancer. To study the importance of MDSC in patients with melanoma, we characterized the frequency, phenotype, and suppressive function of blood myeloid-derived cells and tumor-infiltrating myeloid cells in 26 freshly resected melanomas. Blood and tumor-infiltrating myeloid cells (Lin(-) CD11b(+)) could be phenotypically and morphologically classified into monocytes/macrophages, neutrophils, eosinophils, and immature myeloid cells according to marker expression (CD14(+), CD14(-) CD15(hi), CD14(-) CD15(int), and CD14(-) CD15(-), respectively). In contrast to the expansion of MDSC reported in tumor-bearing mice, we found no differences in the frequency and phenotype of myeloid subsets in the blood of patients with melanoma compared with healthy donors. Myeloid cells represented 12% of the live cells in the melanoma cell suspensions, and were phenotypically diverse with high tumor-to-tumor variability. Interestingly, a positive association was found between the percentage of Tregs and granulocytic cells (Lin(-) CD11b(+) CD14(-)CD15(+)) infiltrating melanoma tumors. However, melanoma-infiltrating myeloid cells displayed impaired suppression of nonspecific T-cell proliferation compared with peripheral blood myeloid cells, in which monocytes and eosinophils were suppressive. Our findings provide a first characterization of the nature and suppressive function of the melanoma myeloid infiltrate and indicate that the suppressive function of MDSC in patients with melanoma seems far less than that based on murine tumor models.