Pyroptosis in Cancer: Friend or Foe?

SIMPLE SUMMARY: Pyroptosis is a new form of programmed cell death that differs from apoptosis in terms of its release of inflammatory factors and its characteristic bubble-like morphology. Pyroptosis was first discovered in the process of immune defense against bacterial infection, but the field of research soon spread to other inflammatory diseases and cancer. As cancer constitutes a serious risk for public health, numerous studies investigating pyroptosis in cancer have been carried out during these years. Tumorigenesis and new therapeutic treatments have been the focus of much recent research. This review discusses the role of pyroptosis in tumorigenesis and its influence on tumor immunity. ABSTRACT: Pyroptosis is an inflammatory form of programmed cell death that is mediated by pore-forming proteins such as the gasdermin family (GSDMs), including GSDMA-E. Upon cleavage by activated caspases or granzyme proteases, the N-terminal of GSDMs oligomerizes in membranes to form pores, resulting in pyroptosis. Though all the gasdermin proteins have been studied in cancer, the role of pyroptosis in cancer remains mysterious, with conflicting findings. Numerous studies have shown that various stimuli, such as pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), and chemotherapeutic drugs, could trigger pyroptosis when the cells express GSDMs. However, it is not clear whether pyroptosis in cancer induced by chemotherapeutic drugs or CAR T cell therapy is beneficial or harmful for anti-tumor immunity. This review discusses the discovery of pyroptosis as well as its role in inflammatory diseases and cancer, with an emphasis on tumor immunity.