Fig. 3. Positive feedback loops involved in pyroptosis and immune response.

Pyroptotic cancer cells release a number of inflammatory factors, which in turn recruit immune cells and enhance the systemic immune response to kill cancer cells. CD4 + T cells, CD8 + T cells and CAR T cells secrete proteins of the granzyme family and perforin. Perforin forms membrane pores in tumour cells, through which granzymes translocate into tumour cells to trigger pyroptosis. Moreover, DAMPs released from the pyroptosis of cancer cells activate macrophages, which release large amounts of IL-6 and IL-1, inducing CRS. The positive feedback loop indicates that only a few cancer cells undergoing pyroptosis activate the immune system, alter the tumour microenvironment, and further trigger cell death.