Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer.
Immunosuppressive CD14+HLA-DRlow/- monocytes in prostate cancer.
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DOI：
10.1002/pros.21078
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发表时间：
2010-03-01
期刊：
影响因子：
2.8
通讯作者：
Dietz, Allan B.
中科院分区：
文献类型：
--
作者：
Vuk-Pavlovic, Stanimir;Bulur, Peggy A.;Lin, Yi;Qin, Rui;Szumlanski, Carol L.;Zhao, Xinghua;Dietz, Allan B.
关键词：
确定循环中髓系来源的抑制细胞水平是否随着前列腺癌(PCa)的进展而增加；确定这些细胞是否可能导致前列腺癌免疫治疗的相对低效。我们分析了未经治疗的PCA患者(18例，平均年龄为72.1±6.9岁)、TPCA患者(22例，72.8±9.8岁)和年龄匹配的对照组(AMC，12例，68.8±7.5岁)的外周血单个核细胞。我们量化了表面标志物的表型、分化潜能、对T细胞增殖的影响和细胞内细胞因子。我们观察到一种髓系来源的抑制细胞，CD14+HLADRlow/−单核细胞在TPCa中的比例(30.7%±15.0%)高于AMC4.1%±6.5%和uPCA(10.6%±14.3%，P=0.0001)。CD14+HLADRlow/−细胞水平与外周血PSA水平以及LHRH激动剂亮丙瑞林联合抗雄激素或地塞米松治疗显著相关。在统计学上，来自TPCA的单核细胞比AMC单核细胞更有效地抑制自体T细胞的增殖，并且其分化为表型成熟树突状细胞的能力存在缺陷。CD14+HLADRlow/−细胞较CD14+HLADR+细胞表达更高水平的IL-10，并更有效地抑制T细胞增殖。这是首次报道CD14+细胞在PCa患者中表现出人类白细胞抗原-DR分子表达减少。这些细胞在体外和体内抑制免疫细胞功能，这一发现必须在为前列腺癌患者设计免疫治疗方案时考虑在内。
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-DRlow/− 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-DRlow/− 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-DRlow/− 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.
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DOI：
10.1089/152581600319676
发表时间：
2000-02-01
期刊：
JOURNAL OF HEMATOTHERAPY & STEM CELL RESEARCH
影响因子：
--
作者：
Dietz, AB;Bulur, PA;Vuk-Pavlovic, S
通讯作者：
Vuk-Pavlovic, S
CD127表达与FOXP3和人类CD4+ T Reg细胞的抑制功能成反比。
DOI：
10.1084/jem.20060772
发表时间：
2006-07-10
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
11.2
作者：
Degl'Innocenti, Elena;Grioni, Matteo;Bellone, Matteo
通讯作者：
Bellone, Matteo
影响因子：
4.4
作者：
Almand, B;Clark, JI;Gabrilovich, DI
通讯作者：
Gabrilovich, DI
影响因子：
--
作者：
KYPRIANOU, N;ISAACS, JT
通讯作者：
ISAACS, JT