The present disclosure relates to erythroid cells that have been engineered to include, e.g., at the surface of the cell, one or more exogenous stimulatory polypeptides, wherein the exogenous stimulatory polypeptides presented are sufficient to stimulate an immune killer cell. The engineered enucleated cells of the present disclosure are useful in methods of activating NK cells and/or CD8+T-cells in a subject in need thereof, such as subjects having cancer or an infectious disease, and in particular cancers or infectious diseases characterized by downregulation of MHC Class I presentation.