M2 type Macrophages promote OSCC progress via conferring resistance to Erastin-induced ferroptosis

Abstract Introduction. M2 type macrophages could promote oral squamous cell carcinoma (OSCC) progress. Ferroptosis is a newly discovered type of programmed cell death and inhibition of ferroptosis in many tumor models could promote tumor progression. This study aims to investigate whether M2 type macrophages could influence the progression of OSCC by regulating the ferroptosis of tumor cells. Methods. Immunohistochemical staining was performed to verify the correlation between the expression of CD206 representing M2 type macrophage infiltration in tumor tissue, and GPX4 representing the ability to resist ferroptosis in vivo. In vitro, treat OSCC cells with ferroptosis inducers at different concentrations, detect their effects on ferroptosis, and meanwhile observe their impacts on the proliferation, migration and invasion abilities of OSCC cells; stimulate macrophages to generate different polarization states and identify them. Then, OSCC cells with different levels of ferroptosis were treated with products from macrophages of different polarized states, and the effects on ferroptosis and proliferation, migration and invasion ability of OSCC cells were observed and detected. Results. CD206 and GPX4 expression in OSCC clinical samples were positively correlated. With the downregulation of ferroptosis, the proliferation, migration and invasion of OSCC cells were inhibited, and M2 type macrophages can upregulate ferroptosis of OSCC cells, meanwhile enhancing their proliferation, migration and invasion capacity. Conclusions. Our studies demonstrated M2 type macrophages could accelerate the progression of OSCC by augmenting the capacity of OSCC cells to resist ferroptosis. Clinical Significance. Our studies might offer insights for the application of ferroptosis or macrophage polarization in the therapy of OSCC.