Z Zhang, Judy Lieberman
The major effector cells of antitumor immunity are killer lymphocytes that recognize and eliminate tumor cells. The fact that tumor cells look a lot like normal cells poses a challenge to antitumor immune control. A danger signal from the tumor or from antigen-presenting cells that have taken up dying tumor cells is needed to distinguish tumor cells from normal cells to fully activate killer cell effector functionality and memory and thereby control the tumor. How a tumor cell dies strongly affects whether the immune system sees it as dangerous. Activation of innate immunity in the tumor, including interferon signaling and necrotic cell death (e.g., necroptosis and pyroptosis), sounds a potent immune alarm. Pyroptosis plays an important role in tumor immunity by generating an inflamed tumor microenvironment. However, it is a double-edged sword that can both promote tumorigenesis and increase the effectiveness and cytotoxicity of cancer therapy. In this article, we review what is known about the role of tumor cell pyroptosis, which is arguably the most inflammatory type of cell death, in antitumor immunity and discuss whether it could be safely harnessed to broaden the range of tumors that respond to immunotherapy.