Zero-valent-iron nanoparticles (ZVI-NP) enhanced anti-tumor immunity by re-polarizing pro-tumor M2 macrophages to anti-tumor M1 macrophages, reducing the number of Treg, downregulating PD-1 and CTLA4 on CD8+ T cells to enhance their cytolytic activity against cancer cells, and reducing expression of PD-L1 on the tumor (278). Here, PDCD1 is linked to cancer.