This was further supported by the in vivo xenograft studies that a functional Fc was required for trastuzumab to induce HER2 downregulation, as the trastuzumab variant scIgG-T was unable to mediate HER2 downregulation due to the lack of FcγR engagement on immune cells in the tumor microenvironment. This evidence concerns the gene FCGR2A and neoplasm.