Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
Cancer Immunol Immunother. 2011 Feb;60(2):197-206. doi: 10.1007/s00262-010-0927-9. Epub 2010 Oct 26.
We have previously shown that the suppressive function of regulatory T cells (Tregs) from peripheral blood mononuclear cells (PBMCs) is enhanced in patients with prostate cancer when compared with healthy individuals. Two phase II studies using the PSA-TRICOM vaccine in patients with metastatic castration-resistant prostate cancer (mCRPC) showed evidence of patient benefit in terms of enhanced survival. The Halabi nomogram has been used to predict survival (HPS) of patients with mCRPC treated with conventional chemotherapy or second-line hormonal therapy. Tregs from PBMCs of patients (n = 23) with mCRPC were obtained pre- and post-three monthly vaccinations, and analyzed for number, phenotype, and suppressive function. Changes post- versus pre-vaccination in these parameters were compared with 3-year survival and HPS. No differences in Treg numbers were observed post- versus pre-vaccination. Trends (P = 0.029) were observed between overall survival (OS) and a decrease in Treg suppressive function post- versus pre-vaccination. Trends were also observed in analyzing effector:Treg (CD4(+)CD25(+)CD127(-)FoxP3(+)CTLA4(+)) ratio post- versus pre-vaccination with OS versus HPS. These data provide preliminary evidence for a possible association between improved OS and a decrease in Treg function when PBMCs are analyzed after three monthly vaccinations. Patients with an OS > HPS were more likely to have decreased Treg function following vaccine. Larger studies to confirm and extend these findings are warranted.
我们之前已经表明，与健康个体相比，前列腺癌患者外周血单核细胞（PBMC）中的调节性 T 细胞（Tregs）的抑制功能增强。两项使用 PSA-TRICOM 疫苗治疗转移性去势抵抗性前列腺癌（mCRPC）患者的 II 期研究表明，在增强生存方面，患者受益。Halabi 列线图已用于预测接受常规化疗或二线激素治疗的 mCRPC 患者的生存（HPS）。从 mCRPC 患者（n=23）的 PBMC 中获得 Tregs，在三次每月接种前和接种后进行分析，以分析数量、表型和抑制功能。将接种前后这些参数的变化与 3 年生存率和 HPS 进行比较。接种前后 Treg 数量无差异。观察到总体生存（OS）与接种前后 Treg 抑制功能下降之间存在趋势（P=0.029）。在分析接种前后效应物：Treg（CD4+CD25+CD127-FoxP3+CTLA4+）比值与 OS 与 HPS 之间也观察到趋势。这些数据初步提供了在进行三个月接种后分析 PBMC 时，OS 改善与 Treg 功能下降之间可能存在关联的证据。OS 大于 HPS 的患者在接种后 Treg 功能下降的可能性更大。需要更大的研究来证实和扩展这些发现。
