With this study, we have illustrated that the cancer microenvironment preserved in the PDS, promotes a distinctive cancer cell – T cell interaction not present in monolayer cultures by influencing T cell activation, increasing the percentage of CD69+ and PD-1+ T cells, contributing to PD-L1 induction in MCF-7 cancer cells and affecting the cancer cells susceptibility to T cell killing, including the efficacy of the immune checkpoint inhibitor Pembrolizumab. This evidence concerns the gene CD69 and cancer.