CDDO-ME Activates NRF2 to Inhibit The Pro-Invasion Ability of TAMs

Background: Tumor-associated macrophages can account for more than 50% of the cells in the tumor immune microenvironment of breast cancer patients. A high TAM density is related to a poor clinical prognosis. Targeting TAMs is a promising therapeutic strategy since TAMs promote tumor growth, development and metastasis. Results: We found that CDDO-ME significantly inhibited the tumor invasion-promoting ability of TAMs in the coculture system and further showed that CDDO-ME functioned by reducing ROS production in TAMs. The orthotopic 4T1 cell inoculation model and spontaneous MMTV-PyMT tumor model were used to evaluate the antitumor effect of CDDO-ME. The results showed that CDDO-ME significantly inhibited tumor metastasis and increased T cell infiltration into the tumor microenvironment. Mechanistically, NRF2 activation was necessary for CDDO-ME to exert its function. Conclusions: Overall, CDDO-ME can play a role in breast cancer as an anticancer drug targeting TAMs.