Cesana Giovanni C, DeRaffele Gail, Cohen Seth, Moroziewicz Dorota, Mitcham Josephine, Stoutenburg John, Cheung Ken, Hesdorffer Charles, Kim-Schulze Seunghee, Kaufman Howard L
Tumor Immunology Laboratory, Department of Surgery and Biostatistics, Columbia University Medical Center, New York, NY 10032, USA.
J Clin Oncol. 2006 Mar 1;24(7):1169-77. doi: 10.1200/JCO.2005.03.6830.
To characterize the number and functional status of CD4+CD25+ regulatory T cells (Tregs) in patients with metastatic melanoma (MM) and renal cell carcinoma (RCC) treated with high-dose bolus interleukin-2 (IL-2).
Patients with MM or RCC treated with high-dose bolus IL-2 (600,000 IU/kg every 8 hours) at a single center provided pre- and post-treatment whole blood specimens. Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, separated into cellular subsets, and analyzed by flow cytometry or used for in vitro proliferation assays.
Between September 2003 and July 2005 57 patients were enrolled in the study with 48 patients available for analysis (45 MM, 12 RCC). Tregs were defined as CD4+CD25(hi) T cells, and this subset was significantly elevated in the cancer patients compared with normal donors (7.75% v 2.24%). The CD4(+)CD25(hi) T-cell pool in the patients constitutively expressed intracellular FoxP3, CTLA-4, and produced high amounts of IL-10. The Tregs were CCR7+ with 50% representing naïve and 50% central-memory T cells. The cells were functionally suppressive in mixed in vitro proliferation assays. Following IL-2 administration, the number and frequency of Tregs increased in patients with progressive disease but returned to normal levels in patients with objective clinical responses.
The number of Tregs, defined as CD4+CD25(hi) T cells is increased in patients with MM and RCC. High-dose IL-2 resulted in a significant decrease of Tregs in those patients achieving an objective clinical response to IL-2 therapy.
对接受大剂量推注白细胞介素-2（IL-2）治疗的转移性黑色素瘤（MM）和肾细胞癌（RCC）患者体内CD4+CD25+调节性T细胞（Tregs）的数量和功能状态进行特征描述。
在单一中心接受大剂量推注IL-2（每8小时600,000 IU/kg）治疗的MM或RCC患者提供治疗前和治疗后的全血标本。通过Ficoll密度梯度离心法分离外周血单个核细胞，将其分为细胞亚群，并通过流式细胞术进行分析或用于体外增殖试验。
2003年9月至2005年7月期间，57例患者纳入本研究，48例患者可供分析（45例MM，12例RCC）。Tregs被定义为CD4+CD25（高表达）T细胞，与正常供体相比，该亚群在癌症患者中显著升高（7.75%对2.24%）。患者体内的CD4(+)CD25(高表达) T细胞库组成性表达细胞内FoxP3、CTLA-4，并产生大量IL-10。Tregs为CCR7+，其中50%为初始T细胞，50%为中央记忆T细胞。在体外混合增殖试验中，这些细胞具有功能抑制作用。给予IL-2后，疾病进展患者的Tregs数量和频率增加，但在有客观临床反应的患者中恢复到正常水平。
MM和RCC患者中，定义为CD4+CD25（高表达）T细胞的Tregs数量增加。大剂量IL-2导致对IL-2治疗有客观临床反应的患者体内Tregs显著减少。
