We here provide evidence on the immunomodulatory effect of the combined treatment with low doses of IFN-γ + TNF-α, which significantly enhances NK cell-infiltration into 3D BC spheroids and NK cell-mediated killing of BC cells, on the one hand by increasing the expression of death receptors such as FAS and TRAIL-R2 and the adhesion molecule ICAM-1 on BC cells cultured in both 2D and 3D conditions and, on the other hand, by increasing the expression of activating receptors on NK cells infiltrating BC spheroids. This evidence concerns the gene IFNG and breast cancer.