Department of Surgery, School of Medicine, University of Colorado Denver Anschutz Medical Campus, Academic Office One, Mailstop C313, 12631 E. 17th Ave, Aurora, CO, 80045, USA.
Cancer Immunol Immunother. 2013 Nov;62(11):1711-22. doi: 10.1007/s00262-013-1475-x. Epub 2013 Sep 27.
Myeloid-derived suppressor cells are increased in the peripheral blood of advanced-stage cancer patients; however, no studies have shown a correlation of these immunosuppressive cells with clinical outcomes in melanoma patients. We characterized the frequency and suppressive function of multiple subsets of myeloid-derived suppressor cells in the peripheral blood of 34 patients with Stage IV melanoma, 20 patients with Stage I melanoma, and 15 healthy donors. The frequency of CD14+ MDSCs (Lin- CD11b+ HLA-DR- CD14+ CD33+) and CD14- MDSCs (Lin- CD11b+ HLA-DR- CD14- CD33+) was increased in the peripheral blood of Stage IV melanoma patients relative to healthy donors. The frequency of CD14+ and CD14- MDSCs correlated with each other and with the increased frequency of regulatory T cells, but not with classically defined monocytes. CD14- MDSCs isolated from the peripheral blood of Stage IV melanoma patients suppressed T cell activation more than those isolated from healthy donors, and the frequency of these cells correlated with disease progression and decreased overall survival. Our study provides the first evidence that the frequency of CD14- MDSCs negatively correlates with clinical outcomes in advanced-stage melanoma patients. These data indicate that suppressive MDSCs should be considered as targets for future immunotherapies.
髓系来源的抑制性细胞在晚期癌症患者的外周血中增加；然而，尚无研究表明这些免疫抑制细胞与黑色素瘤患者的临床结局相关。我们在 34 名 IV 期黑色素瘤患者、20 名 I 期黑色素瘤患者和 15 名健康供体的外周血中，对多种髓系来源的抑制性细胞亚群的频率和抑制功能进行了表征。与健康供体相比，IV 期黑色素瘤患者外周血中 CD14+ MDSC（Lin-CD11b+HLA-DR-CD14+CD33+）和 CD14-MDSC（Lin-CD11b+HLA-DR-CD14-CD33+）的频率增加。CD14+和 CD14-MDSC 的频率彼此相关，且与调节性 T 细胞的频率增加相关，但与经典定义的单核细胞无关。从 IV 期黑色素瘤患者外周血中分离出的 CD14-MDSC 比从健康供体中分离出的 CD14-MDSC 更能抑制 T 细胞活化，并且这些细胞的频率与疾病进展和总生存期缩短相关。我们的研究首次提供了证据，表明 CD14-MDSC 的频率与晚期黑色素瘤患者的临床结局呈负相关。这些数据表明，抑制性 MDSC 应被视为未来免疫疗法的靶点。
