Fig. 4

Copper and cuproptosis in the tumor microenvironment. Copper exhibits a biphasic regulatory role in T cells. Moderate copper levels promote T cell activation, exemplified by copper oxide nanoparticles (CuO NPs). However, excessive copper inhibits the activation of both T and NK cells via the JAK/STAT and EGFR signaling pathways. Copper-based nanoparticles, nanovaccines, and elesclomol-Cu promote the polarization of tumor-associated macrophages (TAMs) toward the M1 phenotype, thereby activating T cells and inducing dendritic cell (DC) maturation. Copper boosts neutrophil function by increasing cell deformability and chemotaxis. Neutrophil membrane-coated nanoparticles induce cuproptosis and ferroptosis in tumors while evading immune detection. The copper chelator CuNG induces myeloid-derived suppressor cell (MDSC) apoptosis and shifts CD4⁺ T cells toward Th1 phenotypes, thus enhancing immune activation. Copper-based therapies multifacetedly impact DCs via antigen release, IL-8, and the cGAMP/cGAS-STING pathway to boost antitumor immunity