ERBB2 and cancer: To test whether the interaction between trastuzumab Fc and FcγRs on immune cells is required for HER2 downregulation in cancer cells, we used three variants of trastuzumab with compromised or no Fc functions [25,29,30]: the scIgG-T variant has a single proteolytic cleavage at the hinge region of trastuzumab; the N297A-T has one amino acid mutation at the position 297 (from N to A, European numbering) and lacks N-glycosylation and Fc function; and the F(ab’)2-T was generated by cleavage of trastuzumab Fc with the protease pepsin.