Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival
Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival
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DOI：
10.1038/nm1093
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发表时间：
2004-09-01
期刊：
影响因子：
82.9
通讯作者：
Zou, WP
中科院分区：
文献类型：
--
作者：
Curiel, TJ;Coukos, G;Zou, WP
调节性T（T-reg）细胞通过抑制自身反应性T细胞来介导外周免疫稳态耐受。宿主抗肿瘤免疫的失败可能是由T-reg细胞对肿瘤相关抗原反应性淋巴细胞的过度抑制所致；然而，缺乏T-reg细胞在人类癌症中具有免疫病理作用的确凿证据。在此，我们通过对104名卵巢癌患者的CD4(+)CD25(+)FOXP3(+) T-reg细胞的详细研究表明，人类肿瘤T-reg细胞抑制肿瘤特异性T细胞免疫，并在体内促进人类肿瘤的生长。我们还表明，肿瘤T-reg细胞与高死亡风险和生存率降低相关。人类T-reg细胞优先迁移并聚集在肿瘤和腹水中，但在癌症晚期很少进入引流淋巴结。肿瘤细胞和微环境中的巨噬细胞产生趋化因子CCL22，它介导T-reg细胞向肿瘤的迁移。T-reg细胞的这种特异性募集代表了肿瘤可能促进免疫豁免的一种机制。因此，阻断T-reg细胞的迁移或功能可能有助于攻克人类癌症。
Regulatory T (T-reg) cells mediate homeostatic peripheral tolerance by suppressing autoreactive T cells. Failure of host antitumor immunity may be caused by exaggerated suppression of tumor-associated antigen - reactive lymphocytes mediated by T-reg cells; however, definitive evidence that T-reg cells have an immunopathological role in human cancer is lacking. Here we show, in detailed studies of CD4(+) CD25(+) FOXP3(+) T-reg cells in 104 individuals affected with ovarian carcinoma, that human tumor T-reg cells suppress tumor-specific T cell immunity and contribute to growth of human tumors in vivo. We also show that tumor T-reg cells are associated with a high death hazard and reduced survival. Human T-reg cells preferentially move to and accumulate in tumors and ascites, but rarely enter draining lymph nodes in later cancer stages. Tumor cells and microenvironmental macrophages produce the chemokine CCL22, which mediates trafficking of T-reg cells to the tumor. This specific recruitment of T-reg cells represents a mechanism by which tumors may foster immune privilege. Thus, blocking T-reg cell migration or function may help to defeat human cancer.