Therefore, our study suggests novel approaches to improving trastuzumab efficacy in HER2-positive breast cancer patients, e.g., antibody- or CRISPR/Cas9-mediated depletion of HLA-G, or development of soluble KIR2DL4 or blockers for the HLA-G/KIR2DL4 interaction. Here, KIR2DL4 is linked to breast cancer.