CTLA4 and cancer: Intriguingly, ZVI NPs also augmented anti-cancer immunity via shifting pro-tumor M2 macrophages to anti-tumor M1, minimizing the population of regulatory T cells, attenuating PD-L1 expression in cancer cells, downregulating PD-1 and cytotoxic T-lymphocyte associated protein 4 in CD8+ T cells, to potentiate their cytolytic activity against cancer cells.