Gasdermin E connects cancer cell DNA sensing to inflammatory cell death linked to effective checkpoint immunotherapy

High transcriptional activity of a pyroptosis gene set in melanoma patients is associated with prolonged survival and better response to immune checkpoint inhibitor therapy.

• Activation of the RIG-I receptor in tumor cells leads to the cleavage of the protein gasdermin E, resulting in cell death through inflammatory pyroptosis.
• Dying tumor cells lose membrane integrity and release their contents, which may enhance the immune response against the tumor.
• The effectiveness of tumor antigen presentation by dendritic cells and the subsequent activation of cytotoxic T cells depend on the activity of gasdermin E within the tumor.
• In preclinical murine cancer models, tumors lacking effective gasdermin E signaling showed resistance to immune checkpoint inhibitors.
• Epigenetic changes that upregulate signaling pathways can make tumor cells more susceptible to inflammatory cell death and improve responses to immunotherapy.
• A strong correlation exists between the genetic activity of RIG-I and pyroptosis pathways in human melanoma samples.

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