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。对曲妥珠单抗介导的ADCC高度敏感的食管SCC细胞系TE 4用曲妥珠单抗介导的ADCC重复处理，并且通过有限稀释克隆存活的肿瘤细胞，并选择为68个逃逸的肿瘤克隆。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对肿瘤克隆的较低敏感性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. Esophageal SCC cell line TE4, which is highly susceptible to Trastuzumab-mediated ADCC, were repeatedly treated with Trastuzumab-mediated ADCC, and the surviving tumor cells are cloned by limited dilution and selected as 68 escaped tumor clones. 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.