Effects of immunorelated gene polymorphisms on trastuzumab targeting breast cancer cell

Abstract

Abstract Purpose Transtuzumab-based immunotherapy has been the standard of care for HER2/neu-expressing breast cancer (BC). However, only 20–30% of patients overexpressing HER2 respond to trastuzumab. This study aimed to investigate the associations between genetic polymorphisms in immunorelated genes and PBMC-induced cytotoxicity to breast cancer cell with the treatment of trastuzumab.Methods Trastuzumab-mediated cytotoxicity of peripheral blood mononuclear cells (PBMC) from 148 healthy donors and 13 BC patients was analyzed by flow cytometry. 16 SNPs in 7 genes (CD247, ZAP70, FCGR2A, FCGR2C, FCGR3C, TNF, and IFNG) were genotyped using the Sequenom Mass Array Genotype Platform. Levels of cytokines were measured with the Th1/Th2Cytokine Kit II.Results Both cytotoxicity and TNF release in the trastuzumab treated PBMCs were significantly higher than those of the basal group, and trastuzumab stimulated cytotoxicity of PBMCs in BC patients as effectively as in healthy donors. A wide variability in trastuzumab-mediated cytotoxicity in 148 healthy donors was observed, and PBMCs from individuals with the CD247 rs16859030 T genotype generated increased cytotoxicity than those with the CD247 rs16859030 CC genotype. We also observed that natural killer cells (NKs) elicited stronger cytotoxicity than PBMCs.Conclusion The CD247 rs16859030 polymorphism affects trastuzumab-mediated cytotoxicity in vitro. Furthermore, trastuzumab-mediated cytotoxicity is not changed in BC patients.