In this study, we investigated the immunomodulatory effects of a combined treatment with low, non-toxic doses of IFN-γ + TNF-α on BC cell lines cultured in two-dimensional (2D) and three-dimensional (3D) spheroids-like patterns, focusing on the expression of ligands for NK cell-activating receptors, death receptors such as FAS and TRAIL-R2, and the adhesion molecule such as ICAM-1. The gene discussed is TNF; the disease is breast cancer.