CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients
CD4+CD25high T cells are enriched in the tumor and peripheral blood of prostate cancer patients
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DOI：
10.4049/jimmunol.177.10.7398
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发表时间：
2006-11-15
影响因子：
4.4
通讯作者：
Pisa, Pavel
中科院分区：
文献类型：
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作者：
Miller, Ashley M.;Lundberg, Kajsa;Pisa, Pavel
在这项研究中，我们调查了接受前列腺切除术的早期前列腺癌患者的肿瘤组织和外周血中CD4(+)CD25(高)调节性T细胞（Treg）是否增加。我们发现，与同一前列腺的良性组织相比，前列腺内CD4(+)CD25(高)T细胞在肿瘤中的患病率显著更高。此外，与正常供体相比，前列腺癌患者外周血中CD4(+)CD25(高)T细胞的频率显著更高。还显示一部分CD4(+)CD25(高)T细胞为糖皮质激素诱导的肿瘤坏死因子受体、诱导性共刺激分子（ICOS）和叉头框蛋白P3（FOXP3）阳性。而且，来自血液的CD4(+)CD25(+)T细胞以及培养的前列腺肿瘤组织样本的上清液在体外表现出免疫抑制功能。此外，培养的前列腺组织样本的上清液和前列腺癌腹水诱导了CD4(+)CD25(+)T细胞的迁移，并且通过酶联免疫吸附测定（ELISA）显示含有调节性T细胞趋化因子CCL22。我们的研究结果表明，Tregs是早期前列腺肿瘤的一个重要细胞成分，因此旨在抑制或清除Tregs的新治疗策略可能会改善前列腺癌的免疫治疗。
In this study, we investigated whether CD4(+)CD25(high) regulatory T cells (Treg) are increased in the tumor tissue and peripheral blood of early-stage prostate cancer patients undergoing prostatectomy. We show that the prevalence of CD4(+)CD25(high) T cells inside the prostate was significantly higher in the tumor compared with benign tissue from the same prostate. Furthermore, the frequency of CD4(+)CD25(high) T cells in peripheral blood was significantly higher in prostate cancer patients compared with normal donors. A proportion of the CD4(+)CD25(high) T cells was also shown to be glucocorticoid-induced TNF receptor, ICOS, and FOXP3 positive. Moreover, CD4(+)CD25(+) T cells from blood and supernatants from cultured prostate tumor tissue samples exhibited immunosuppressive function in vitro. Furthermore, supernatants from cultured prostate tissue samples and prostate cancer ascites fluid induced migration of CD4(+)CD25(+) T cells and were shown to contain the regulatory T cell chemokine CCL22 by ELISA. Our findings indicate that Tregs are an important cellular component of early-stage prostate tumors, and thus new therapeutic strategies aimed at inhibition or depletion of Tregs may improve prostate cancer immunotherapy.