Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Int J Cancer. 2013 Jul 15;133(2):373-82. doi: 10.1002/ijc.28026. Epub 2013 Feb 12.
A higher frequency of regulatory T cells (Tregs) has been observed in peripheral blood mononuclear cells (PBMC) of patients with different types of solid tumors and hematological malignancies as compared to healthy donors. In prostate cancer patients, Tregs in PBMC have been shown to have increased suppressive function. Tumor-induced biological changes in Tregs may enable tumor cells to escape immunosurveillance. We performed genome-wide expression analyses comparing the expression levels of more than 38,500 genes in Tregs with similar suppressive activity, isolated from the peripheral blood of healthy donors and patients with metastatic castration-resistant prostate cancer (mCRPC). The differentially expressed genes in mCRPC Tregs are involved in cell cycle processes, cellular growth and proliferation, immune responses, hematological system development and function and the interleukin-2 (IL-2) and transforming growth factor-β (TGF-β) pathways. Studies revealed that the levels of expression of genes responsible for T-cell proliferation (C-FOS, C-JUN and DUSP1) and cellular migration (RGS1) were greater in Tregs from mCRPC patients as compared to values observed in healthy donors. Increased RGS1 expression in Tregs from mCRPC patients suggests a decrease in these Tregs' migratory ability. In addition, the higher frequency of CD4(+) CD25(high) CD127(-) Tregs in the peripheral blood of mCRPC patients may be the result of an increase in Treg proliferation capacity. Results also suggest that the alterations observed in gene expression profiles of Tregs in mCRPC patients may be part of the mechanism of tumor escape from host immune surveillance.
与健康供体相比，不同类型实体瘤和血液恶性肿瘤患者的外周血单个核细胞（PBMC）中观察到调节性 T 细胞（Treg）的频率更高。在前列腺癌患者中，已显示 PBMC 中的 Treg 具有增强的抑制功能。Treg 中的肿瘤诱导的生物学变化可能使肿瘤细胞能够逃避免疫监视。我们进行了全基因组表达分析，比较了来自健康供体和转移性去势抵抗性前列腺癌（mCRPC）患者的外周血中具有相似抑制活性的 Treg 中超过 38500 个基因的表达水平。mCRPC Treg 中差异表达的基因参与细胞周期过程、细胞生长和增殖、免疫反应、血液系统发育和功能以及白细胞介素-2（IL-2）和转化生长因子-β（TGF-β）途径。研究表明，与健康供体相比，mCRPC 患者 Treg 中负责 T 细胞增殖（C-FOS、C-JUN 和 DUSP1）和细胞迁移（RGS1）的基因表达水平更高。mCRPC 患者 Treg 中 RGS1 表达增加表明这些 Treg 迁移能力下降。此外，mCRPC 患者外周血中 CD4(+) CD25(high) CD127(-) Treg 的频率增加可能是 Treg 增殖能力增加的结果。结果还表明，mCRPC 患者 Treg 中观察到的基因表达谱改变可能是肿瘤逃避宿主免疫监视的机制的一部分。
