Fig. 3

Crosstalk between ferroptosis and pyroptosis and antitumor immunity. Pyroptosis in less than 15% of tumor cells is sufficient to clear an entire tumor graft, suggesting that robust anticancer immunity plays an important role in pyroptosis-initiated tumor killing. On the one hand, tumor cells undergoing pyroptosis facilitate the recruitment of anticancer immune cells, including CD8+ T cells and NK cells, by releasing danger signals. However, the level of infiltration of tumor-promoting cells, such as MDSCs, is significantly decreased during this process. On the other hand, CD8+ T cells and NK cells induce cancer cell pyroptosis by secreting GzmA and GzmB, which are enzymes capable of cleaving GSDMB and GSDME, respectively. Activated macrophage-derived IL-1β is required for the antitumor immunity induced by tumor cell pyroptosis. Similarly, CD8+ T cells induce tumor cell ferroptosis by secreting IFN-γ, which mediates the downregulation of SLC7A11 and leads to the accumulation of lipid ROS. Notably, PD1/PDL-1 inhibitors exert an obvious synergistic effect with pyroptosis/ferroptosis inducers on tumor inhibition