Tumor regulatory T cells potently abrogate antitumor immunity.

Tumor regulatory T cells potently abrogate antitumor immunity.
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DOI:
10.4049/jimmunol.0802664
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发表时间:
2009-05-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
You Z
You Z
中科院分区:
其他
文献类型:
--
作者:
Liu Z;Kim JH;Falo LD Jr;You Z

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患有乳腺肿瘤的小鼠的 Treg 升高(肿瘤 Treg)。在体外,虽然肿瘤 Treg 抑制肿瘤引发的 CD4+ T 细胞活性的能力与来自幼稚小鼠的 Treg (naïve Treg) 相当,但只有肿瘤 Treg 抑制幼稚 CD8+ T 细胞激活和 DC 功能。肿瘤 Treg 和幼稚 Treg 都不能在过继转移的肿瘤引发的 CD4+ T 细胞诱导的免疫反应效应阶段抑制抗肿瘤免疫。这与在该模型中观察到的结果一致,即肿瘤 Treg 和幼稚 Treg 都不能在体外或体内抑制效应子。然而,肿瘤 Treg 在 TDLN 中消除肿瘤特异性 CD8+ T 细胞反应,并在过继转移的肿瘤引发的 CD4+ T 细胞诱导的免疫反应早期阶段消除抗肿瘤免疫。这些数据表明,在该模型中,肿瘤 Treg 有效消除 TDLN 中肿瘤特异性 CD8+ T 细胞反应,从而在过继转移的肿瘤引发的 CD4+ T 细胞诱导的免疫反应早期阶段抑制抗肿瘤免疫。
Treg from mice bearing a breast tumor were elevated (tumor Treg). In vitro, whereas tumor Treg ability to inhibit tumor-primed CD4+ T cell activity is comparable to Treg from naïve mice (naïve Treg), only tumor Treg suppress naïve CD8+ T cell activation and DC function. Neither tumor Treg nor naïve Treg can suppress antitumor immunity at the effector phase of the immune response induced by adoptively-transferred tumor-primed CD4+ T cells. This is consistent with the observation that, in this model, neither tumor Treg nor naïve Treg can inhibit effectors in vitro or in vivo. However, tumor Treg abrogate tumor-specific CD8+ T cell responses in TDLN and antitumor immunity at the early stage of the immune response induced by adoptively-transferred tumor-primed CD4+ T cells. These data indicate that, in this model, tumor Treg potently abrogate tumor-specific CD8+ T cell responses in TDLN, thereby suppressing antitumor immunity at the early stage of the immune response induced by adoptively-transferred tumor-primed CD4+ T cells.
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