CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies -: Possible involvement of regulatory T cells in disease progression
CD4+CD25+ regulatory T cells in patients with gastrointestinal malignancies -: Possible involvement of regulatory T cells in disease progression
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DOI：
10.1002/cncr.11618
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发表时间：
2003-09-01
期刊：
影响因子：
6.2
通讯作者：
Takabayashi, A
中科院分区：
文献类型：
--
作者：
Sasada, T;Kimura, M;Takabayashi, A
背景。 CD4(+)CD25(+)调节性T细胞的主动抑制在下调T细胞对外来和自身抗原的反应中起着重要作用。小鼠实验性肿瘤模型表明，调节性 T 细胞可抑制抗肿瘤免疫反应。本研究的目的是证明CD4(+)CD25(+)调节性T细胞可能参与胃肠道恶性肿瘤患者免疫系统损伤。对 149 例胃肠道恶性肿瘤患者的外周血和 7 例腹膜播散患者的腹水中的淋巴细胞表型，特别是 CD4(+)CD25(+) T 细胞的表型进行了分析。此外，对从恶性疾病患者分离的CD4(+)CD25(+)和CD4(+)CD25(-) T细胞进行体外刺激后细胞因子的产生进行了检查。 结果。与健康志愿者相比，胃肠道恶性肿瘤患者外周血中CD4(+)CD25(+) T细胞的比例较高，因为CD4(+)CD25(-) T细胞的数量明显减少。在胃癌患者中，CD4+CD25+T细胞百分比较高的患者预后较差。 CD4(+)CD25(+) T 细胞在晚期腹膜播散患者的腹水中也存在较高比例。从恶性疾病患者分离的 CD4(+)CD25(+) T 细胞产生白细胞介素 (IL)-4 和 IL-10，但不产生 IL-2 或干扰素-γ；这些细胞在体外刺激后还抑制CD4-(+)CD25(-) T细胞产生细胞因子。结论。 CD4(+)CD25(+)调节性T细胞的相对增加可能与胃肠道恶性肿瘤患者的免疫抑制和肿瘤进展有关。这一发现表明，使用免疫调节疗法治疗胃肠道恶性肿瘤患者可能是一种有效的策略。 (C) 2003 年美国癌症协会。
BACKGROUND. Active suppression by CD4(+)CD25(+) regulatory T cells plays an important role in the down-regulation of the response of T cells to foreign and self antigens. Experimental tumor models in mice revealed that regulatory T cells inhibit antitumor immune responses. The purpose of the current study was to demonstrate the possible involvement of CD4(+)CD25(+) regulatory T cells in immune system impairment in patients with gastrointestinal malignancies.METHODS. The phenotypes of lymphocytes, particularly those of CD4(+)CD25(+) T cells, were analyzed in peripheral blood in 149 patients with gastrointestinal malignancies and in ascites in 7 patients with peritoneal dissemination. In addition, cytokine production after in vitro stimulation was examined in CD4(+)CD25(+) and CD4(+)CD25(-) T cells isolated from patients with malignant disease.RESULTS. Compared with healthy volunteers, patients with gastrointestinal malignancies had a higher proportion of CD4(+)CD25(+) T cells in peripheral blood, due to the presence of a drastically smaller number of CD4(+)CD25(-) T cells. Among patients with gastric carcinoma, those with higher percentages of CD4(+)CD25(+) T cells had a poorer prognosis than did those with lower percentages. CD4(+)CD25(+) T cells also were present in greater proportions in ascites from patients who had advanced-stage disease with peritoneal dissemination. Isolated CD4(+)CD25(+) T cells from patients with malignant disease produced interleukin (IL)-4 and IL-10 but not IL-2 or interferon-gamma; these cells also inhibited cytokine production by CD4-(+)CD25(-) T cells after in vitro stimulation.CONCLUSIONS. The relative increase in CD4(+)CD25(+) regulatory T cells may be related to immunosuppression and tumor progression in patients with gastrointestinal malignancies. This finding suggests that the use of immunomodulatory therapy to treat patients with gastrointestinal malignancies may be an effective strategy. (C) 2003 American Cancer Society.