Depending on whether normal fibroblasts or CAFs were used in a given 3D model, the following points were evaluated in the present study: (i) a comparison of NK cell killer activity on two-dimensional (2D) and three-dimensional (3D) cultures of tumor or stromal components of BC, (ii) the penetration of NK cells into the spheroid model, and (iii) the modulation of the immune response by stimulation with a combination of IL-2, IL-15, or TGF-β1. Here, TGFB1 is linked to breast cancer.