T cells are crucial for the anti-metastatic effect of anti-epidermal growth factor receptor antibodies
T cells are crucial for the anti-metastatic effect of anti-epidermal growth factor receptor antibodies
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DOI：
10.1007/s00262-007-0313-4
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发表时间：
2007-11-01
影响因子：
5.8
通讯作者：
Fernandez, Luis E.
中科院分区：
文献类型：
--
作者：
Garrido, Greta;Lorenzano, Pablo;Fernandez, Luis E.
表皮生长因子受体（epidermal growth factor receptor，EGFR）是肿瘤转移的重要分子，已有大量实验证据支持其作用。目前，抗EGFR单克隆抗体（mAb）构成了治疗转移性肿瘤患者的一种有前途的方法。然而，由于缺乏适当的同基因临床前模型，与这些mAb的强效抗转移作用相关的机制尚未完全阐明。本文研究了EGFR特异性抗体7A 7对D122小鼠肺癌转移特性的影响。7A 7 mAb通过对肿瘤转移的直接抗增殖和促凋亡作用显著损害C57 BL/ 6小鼠中D122细胞的转移扩散。7A 7 mAb抑制D122细胞上EGFR活化的能力可能有助于其抗转移eVect。此外，7A 7 mAb能够在体外诱导抗体依赖性细胞介导的对D122细胞的细胞毒性。有趣的是，7A 7 mAb治疗增加了浸润转移部位的自然杀伤细胞、T淋巴细胞和树突状细胞的数量。更引人注目的是，体内CD 8+和CD 4 + T细胞的消耗完全消除了7A 7 mAb的抗转移活性，而自然杀伤细胞的功能是不相关的。该研究支持T细胞应答在抗EGFR mAb的作用机制中的体内作用，表明佐剂eVect的诱导。
Experimental evidences supporting the epidermal growth factor receptor (EGFR) as an important molecule for tumor metastasis had been accumulated. Currently, anti-EGFR monoclonal antibodies (mAbs) constitute a promising approach for the treatment of patients with metastatic tumors. However, the mechanisms associated with the potent anti-metastatic effect of these mAbs have not been completely elucidated due to the lack of appropriate syngeneic preclinical models. In this paper, we have investigated the effects of 7A7, an antibody specific to murine EGFR, on the metastatic properties of D122 murine lung carcinoma. 7A7 mAb significantly impaired metastatic spread of D122 cells in C57BL/ 6 mice by direct anti- proliferative and proapoptotic effects on tumor metastasis. 7A7 mAb capacity to inhibit EGFR activation on D122 cells could contribute to its anti- metastatic eVect. In addition, 7A7 mAb was able to induce in vitro antibody- dependent cell- mediated cytotoxicity on D122 cells. Interestingly, 7A7 mAb treatment increased the number of natural killer cells, T lymphocytes and dendritic cells infiltrating the metastatic sites. More strikingly, depletion of CD8+ and CD4+ T cells in vivo completely abrogated the 7A7 mAb anti- metastatic activity whereas function of natural killer cells was irrelevant. This study supports an in vivo role for T cell response in the mechanism of action of anti- EGFR mAbs, suggesting the induction of an adjuvant eVect.