Antibody Dependent Cell-Mediated Cytotoxicity Selection Pressure Induces Diverse Mechanisms of Resistance (CITE-Seq). Antibody Dependent Cell-Mediated Cytotoxicity Selection Pressure Induces Diverse Mechanisms of Resistance (CITE-Seq)

Targeted monoclonal antibody therapy has emerged as a powerful therapeutic strategy for cancer. Unfortunately, only a minority of patients haves durable responses and the development of resistance remains a major clinical obstacle. Antibody-dependent cell-mediated cytotoxicity (ADCC) represents a crucial therapeutic mechanism of action; however few studies have explored ADCC resistance. Using multiple in vitro models of ADCC selection pressure, we have uncovered both shared and distinct resistance mechanisms. We employed CITE sequencing and single-cell ATAC-seqeuncing to interrogate molecular mechanisms of resistance. Overall design: Comparative gene and protein expression profiling analysis of CITE-seq data for A431, FaDu, and SKOV3 cell lines, both sensitive to and with acquired resistance to ADCC

靶向单克隆抗体疗法（targeted monoclonal antibody therapy）已成为癌症治疗领域一种强有力的治疗策略。然而仅有少数患者能够获得持久应答，而耐药性的产生仍是临床面临的主要障碍。抗体依赖性细胞介导的细胞毒性（Antibody-dependent cell-mediated cytotoxicity，ADCC）是一类关键的治疗作用机制，但目前针对ADCC耐药性的相关研究仍较为匮乏。本研究通过多种施加ADCC筛选压力的体外模型，揭示了兼具共性与特异性的耐药机制。我们采用CITE测序（CITE sequencing）与单细胞ATAC测序（single-cell ATAC sequencing）来解析耐药性的分子机制。整体实验设计：对ADCC敏感型及获得性ADCC耐药的A431、FaDu与SKOV3细胞系的CITE-seq数据开展基因与蛋白质表达谱的比较分析。