目前赫赛汀是HER2阳性乳腺癌的一线用药，但赫赛汀的原发性或继发性耐药是临床上遇到的棘手问题。我们发现，赫赛汀通过ADCC效应杀瘤的同时存在一个副反应，即赫赛汀促进NK细胞-肿瘤细胞cell-in-cell的形成，参与肿瘤细胞对NK细胞的胞内反杀及获得新生物学特征的过程，最终导致肿瘤的免疫逃逸和赫赛汀耐药。Cell-in-cell（细胞叠套）是指效应细胞进入靶细胞并产生生物学效应的过程，是一种特殊的细胞相互作用模式。本课题从赫赛汀通过NK细胞起作用的方式ADCC效应入手，发现NK细胞-肿瘤细胞相互作用的特殊模式cell-in-cell介导赫赛汀耐药为新的突破点，探讨赫赛汀参与肿瘤细胞反杀NK细胞和获得新特征的分子机制并以此提出可能的解决方案处理赫赛汀耐药，为解析赫赛汀耐药提供独具特色的研究切入点，也为赫赛汀对HER2阳性乳腺癌的治疗提供新策略，具有重要的基础和临床研究价值。

Herceptin, a HER2-targeted monoclonal antibody drug, has been applied extensively in clinical practices. Despite significant improvement in the clinical outcome of HER2+ breast cancer since primary drug resistance and secondary drug resistance. Preclinical and clinical observations indicate that triggering of NK cell-mediated ADCC is one of the mechanisms accounting for Herceptin therapeutic activity. Currently, we found an unexpected finding that Herceptin mediated cell-in-cell process between NK cells and tumor cells, subsequently tumor cells killed NK cell inside and acquired new biological features, which is considered an important process for tumor immune escape and drug resistant. Cell-in-cell (CIC) refers to one or more viable cells existing inside another one, which is an unusual interactive model between immune cells and tumor cells. Based on the tumoricidal effects of Herceptin via ADCC by NK cells, we intend to highlight the possibility that Herceptin promotes cell-in-cell formation between NK cells and tumor cells, leads to tumor cells killing NK cells and acquiring new biological features, and the subsequent triggering immune escape and drug resistance of tumor cells. To dissect the exact mechanisms of Herceptin mediated cell-in-cell process and its significance will provide new theory to elucidate Herceptin resistance, as well as therapy strategy for the HER2+ breast cancer.