Velmurugan Ramraj, Challa Dilip K, Ram Sripad, Ober Raimund J, Ward E Sally
Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas. Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas. Biomedical Engineering Graduate Program, University of Texas Southwestern Medical Center, Dallas, Texas. Department of Immunology, UT Southwestern Medical Center, Dallas, Texas.
Department of Immunology, UT Southwestern Medical Center, Dallas, Texas.
Mol Cancer Ther. 2016 Aug;15(8):1879-89. doi: 10.1158/1535-7163.MCT-15-0335. Epub 2016 May 25.
Understanding the complex behavior of effector cells such as monocytes or macrophages in regulating cancerous growth is of central importance for cancer immunotherapy. Earlier studies using CD20-specific antibodies have demonstrated that the Fcγ receptor (FcγR)-mediated transfer of the targeted receptors from tumor cells to these effector cells through trogocytosis can enable escape from antibody therapy, leading to the viewpoint that this process is protumorigenic. In the current study, we demonstrate that persistent trogocytic attack results in the killing of HER2-overexpressing breast cancer cells. Further, antibody engineering to increase FcγR interactions enhances this tumoricidal activity. These studies extend the complex repertoire of activities of macrophages to trogocytic-mediated cell death of HER2-overexpressing target cells and have implications for the development of effective antibody-based therapies. Mol Cancer Ther; 15(8); 1879-89. ©2016 AACR.
了解效应细胞（如单核细胞或巨噬细胞）在调节癌性生长中的复杂行为对于癌症免疫治疗至关重要。早期使用CD20特异性抗体的研究表明，通过胞啃作用，Fcγ受体（FcγR）介导的靶向受体从肿瘤细胞转移至这些效应细胞可导致抗体治疗失效，从而形成了该过程具有促肿瘤作用的观点。在本研究中，我们证明持续的胞啃攻击可导致HER2过表达的乳腺癌细胞死亡。此外，通过抗体工程增加FcγR相互作用可增强这种杀肿瘤活性。这些研究将巨噬细胞的复杂活性谱扩展至胞啃介导的HER2过表达靶细胞的细胞死亡，并对开发有效的基于抗体的疗法具有启示意义。《分子癌症治疗》；15(8)；1879 - 89。©2016美国癌症研究协会。
