ERBB2 and cancer: This notion is supported by three pieces of evidence presented in this study: 1) co-culturing cancer cells with immune cells alone did not drive HER2 downregulation in cancer cells; 2) physical separation of cancer cells and PBMCs in the transwell assay abolished the trastuzumab-mediated HER2 downregulation in cancer cells; and 3) trastuzumab variants with compromised Fc function did not induce HER2 downregulation in cancer cells.