Mechanisms of escape from trastuzumab-mediated ADCC in esophageal squamous cell carcinoma.

我们使用食管鳞状细胞癌细胞克隆阐明了逃避曲妥珠单抗介导的ADCC的机制。纯化NK细胞的ADCC试验显示肿瘤细胞克隆对曲妥珠单抗介导的ADCC具有显著敏感性。这些结果表明，对曲妥珠单抗介导的ADCC的敏感性主要是由于对NK细胞介导的ADCC的敏感性差异。此外，分析PFN诱导的透化程度和PFN与GrB组合诱导的肿瘤细胞克隆的凋亡。因此，PFN/GrB对肿瘤克隆的敏感性较低与曲妥珠单抗介导的ADCC降低有关。总之，对穿孔素-颗粒酶系统的敏感性降低是解释曲妥珠单抗介导的ADCC逃逸的重要机制之一。

We elucidated the mechanisms of escape from trastuzumab-mediated ADCC using esophageal squamous cell carcinoma cell clones. The ADCC assay with purified NK cells showed significantly susceptibility to trastuzumab-mediated ADCC in tumor cell clones. These results indicated that the sensitivity to trastuzumab-mediated ADCC was mainly due to the difference in susceptibility to NK cell-mediated ADCC. Furthermore, the degree of permeabilization induced by PFN and apoptosis induced by the combination of PFN with GrB in tumor cell clones was analyzed. As a result, lower sensitivity for PFN/GrB on tumor clones was related to the reduced trastuzumab-mediated ADCC. In conclusion, lower susceptibility to the perforin-granzyme system is one of the important mechanisms explaining escape from trastuzumab-mediated ADCC.