Interaction with Macrophages Alters the Susceptibility of Cancer Cells to Ferroptosis

Ferroptosis is a new type of cell death, ferroptosis has been proposed in 2012. Ferroptosis is induced by the accumulation of lipid peroxides, and increased intracellular ferrous ion levels contribute to ferroptosis. Here, we tried to elucidate the mechanisms of ferroptosis induction in cancer by focusing on the interaction with macrophages which is one of the major cell types in the tumor microenvironment. As a result, we demonstrated that indirect co-culture and direct co-culture of cancer cells (4T1-Luc cells) with macrophages (RAW 264.7 cells) enhanced the susceptibility to ferroptosis induction. In order to apply ferroptosis inducers as a therapeutic option for cancer in the future, these findings suggest the importance to understand the mechanisms of ferroptosis induction considering cell-cell interaction in TME.