The nonclassical histocompatibility antigen HLA-G expressed by breast cancer cells binds to the NK cell receptor KIR2DL4 and, in the presence of cytokines, such as TGF-β and IFN-γ, impairs NK cell cytotoxicity by upregulating PD-L1 on tumor cells and PD-1 on NK cells, making breast cancer cells resistant to trastuzumab 153,154. The gene discussed is IFNG; the disease is breast carcinoma.