CXC chemokine ligand 9/monokine induced by IFN-γ production by tumor cells is critical for T cell-mediated suppression of cutaneous tumors
CXC chemokine ligand 9/monokine induced by IFN-γ production by tumor cells is critical for T cell-mediated suppression of cutaneous tumors
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DOI：
10.4049/jimmunol.178.4.2278
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发表时间：
2007-02-15
影响因子：
4.4
通讯作者：
Fairchild, Robert L.
中科院分区：
文献类型：
--
作者：
Gorbachev, Anton V.;Kobayashi, Hirobito;Fairchild, Robert L.
肿瘤产生的趋化因子在恶性肿瘤生长中的作用仍然知之甚少。我们检索了体内生长的 MCA205 纤维肉瘤和分离的肿瘤细胞克隆，这些克隆在用 IFN-gamma 刺激后产生由 IFN-gamma (Mig) 诱导的 CXCL9/monokine 和 CXCL10/IFN-gamma 诱导蛋白 10，以及产生 IFN-gamma 诱导蛋白 10 但不产生 Mig 的克隆。与产生 Mig 的肿瘤细胞相比，Mig 缺陷型变体在野生型小鼠中作为皮肤肿瘤生长得更具侵略性。表达 Mig 的肿瘤细胞（而非缺乏 Mig 的肿瘤细胞）的生长受到 NK 和 T 细胞活性的抑制。转导 Mig 阴性变体以产生 Mig 的组成型肿瘤细胞产生，导致 T 细胞依赖性肿瘤排斥，并诱导针对 Mig 缺陷肿瘤的保护性肿瘤特异性 CD8(+) T 细胞反应。结果表明，肿瘤来源的 Mig 在 T 细胞介导的皮肤纤维肉瘤反应中发挥着关键作用，并表明 Mig 表达的丧失是肿瘤细胞用来逃避这些反应的机制。
The role of tumor-produced chemokines in the growth of malignancies remains poorly understood. We retrieved an in vivo growing MCA205 fibrosarcoma and isolated tumor cell clones that produce both CXCL9/monokine induced by IFN-gamma (Mig) and CXCL10/IFN-gamma-inducible protein 10 following stimulation with IFN-gamma and clones that produce IFN-gamma-inducible protein 10 but not Mig. The Mig-deficient variants grew more aggressively as cutaneous tumors in wild-type mice than the Mig-producing tumor cells. The growth of Mig-expressing, but not Mig-deficient, tumor cells was suppressed by NK and T cell activity. Transduction of Mig-negative variants to generate constitutive tumor cell production of Mig resulted in T cell-dependent rejection of the tumors and in induction of protective tumor-specific CD8(+) T cell responses to Mig-deficient tumors. The results indicate a critical role for tumor-derived Mig in T cell-mediated responses to cutaneous fibrosarcomas and suggest the loss of Mig expression as a mechanism used by tumor cells to evade these responses.