Stem Cell Laboratory, Mayo Clinic Cancer Center, College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
Prostate. 2010 Mar 1;70(4):443-55. doi: 10.1002/pros.21078.
To determine if the levels of circulating myeloid-derived suppressor cells increase with progression of prostate cancer (PCa); to determine if such cells could contribute to the relative inefficiency of PCa immunotherapy.
We analyzed peripheral blood mononuclear cells isolated from untreated PCa patients (uPCa; N = 18; mean age +/- SD: 72.1 +/- 6.9 years), tPCa (N = 22; 72.8 +/- 9.8 years) and age matched controls (AMC; N = 12; 68.8 +/- 7.5 years). We quantified surface marker phenotype, differentiation potential, effects on T cell proliferation and intracellular cytokines.
We observed an unexpectedly high percentage of a type of myeloid-derived suppressor cells, CD14(+)HLA-DR(low/-) monocytes, in tPCa (30.7 +/- 15.0% of CD14(+) cells) relative to AMC (4.1 +/- 6.5%, P < 0.0001) and uPCa (10.6 +/- 14.3%, P = 0.0001). The levels of CD14(+) HLA-DR(low/-) cells were significantly correlated with circulating PSA levels and treatment with LHRH-agonist leuprolide in combination with either an antiandrogen or dexamethasone. Monocytes from tPCa inhibited autologous T cell proliferation statistically significantly more effectively than AMC monocytes and were defective in their ability to differentiate into phenotypically mature dendritic cells. Isolated CD14(+)HLA-DR(low/-) cells expressed higher levels of intracellular interleukin-10 and suppressed T cell proliferation more effectively than isolated CD14(+)HLA-DR(+) cells.
This is the first report of CD14(+) cells exhibiting reduced expression of HLA-DR molecules in PCa patients. These cells suppress immune cell function in vitro and, plausibly, in vivo, a finding that must be factored into the design of immunotherapy protocols for PCa patients.
确定循环髓源性抑制细胞（MDSC）水平是否随前列腺癌（PCa）的进展而升高；确定这些细胞是否会导致 PCa 免疫治疗的相对低效。
我们分析了未经治疗的 PCa 患者（uPCa；N=18；平均年龄±标准差：72.1±6.9 岁）、转移 PCa（tPCa；N=22；72.8±9.8 岁）和年龄匹配的对照组（AMC；N=12；68.8±7.5 岁）分离的外周血单核细胞。我们定量了表面标记物表型、分化潜能、对 T 细胞增殖和细胞内细胞因子的影响。
我们观察到 tPCa 中一种髓源性抑制细胞，CD14（+）HLA-DR（低/-）单核细胞的比例异常高（占 CD14（+）细胞的 30.7±15.0%），与 AMC（4.1±6.5%，P<0.0001）和 uPCa（10.6±14.3%，P=0.0001）相比。CD14（+）HLA-DR（低/-）细胞的水平与循环 PSA 水平显著相关，并且与 LHRH 激动剂亮丙瑞林联合抗雄激素或地塞米松治疗相关。与 AMC 单核细胞相比，tPCa 来源的单核细胞能更有效地抑制自体 T 细胞增殖，且其分化为表型成熟树突状细胞的能力存在缺陷。分离的 CD14（+）HLA-DR（低/-）细胞表达更高水平的细胞内白细胞介素 10，并且比分离的 CD14（+）HLA-DR（+）细胞更有效地抑制 T 细胞增殖。
这是首例报道 PCa 患者中 CD14（+）细胞 HLA-DR 分子表达降低的报告。这些细胞在体外和推测在体内抑制免疫细胞功能，这一发现必须纳入 PCa 患者免疫治疗方案的设计中。
