Myeloid cells obtained from the blood but not from the tumor can suppress T-cell proliferation in patients with melanoma.
Myeloid cells obtained from the blood but not from the tumor can suppress T-cell proliferation in patients with melanoma.
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DOI：
10.1158/1078-0432.ccr-12-1108
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发表时间：
2012-10-01
期刊：
影响因子：
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通讯作者：
Rosenberg SA
中科院分区：
文献类型：
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作者：
Gros A;Turcotte S;Wunderlich JR;Ahmadzadeh M;Dudley ME;Rosenberg SA
髓源性抑制细胞（Myeloid-derived suppressor cells， MDSC）是一种免疫调节细胞类型，在肿瘤小鼠中扩增，但对其在癌症患者中的免疫抑制作用知之甚少。为了研究MDSC在黑色素瘤患者中的重要性，我们对26例新切除的黑色素瘤中血液髓源性细胞和肿瘤浸润性髓细胞的频率、表型和抑制功能进行了表征。血液和肿瘤浸润性骨髓细胞（Lin - CD11b+）可根据标记物表达（CD14+、CD14 - CD15hi、CD14 - CD15int和CD14 - CD15 -）在表型和形态学上分为单核/巨噬细胞、中性粒细胞、嗜酸性粒细胞和未成熟骨髓细胞。与在荷瘤小鼠中报道的MDSC扩增相反，我们发现黑色素瘤患者血液中骨髓亚群的频率和表型与健康供者相比没有差异。骨髓细胞占黑色素瘤细胞悬液中活细胞的12%，并且具有表型多样性，肿瘤与肿瘤之间具有很高的可变性。有趣的是，发现Tregs和粒细胞（Lin - CD11b+ CD14 - CD15+）浸润黑色素瘤的百分比呈正相关。然而，与外周血髓细胞相比，黑色素瘤浸润的髓细胞对非特异性t细胞增殖的抑制受损，单核细胞和嗜酸性粒细胞受到抑制。我们的研究结果首次描述了黑色素瘤髓系浸润的性质和抑制功能，并表明MDSC在黑色素瘤患者中的抑制功能似乎远不如基于小鼠肿瘤模型的抑制功能。
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− CD15hi, CD14− CD15int, 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.