IRE1α silences dsRNA to prevent taxane-induced pyroptosis in triple-negative breast cancer.

ABSTRACT: Chemotherapy is often combined with immune checkpoint inhibitor (ICIs) to enhance immunotherapy responses. Despite the approval of chemo-immunotherapy in multiple human cancers, many immunologically cold tumors remain unresponsive. The mechanisms determining the immunogenicity of chemotherapy are elusive. Here, we identify the ER stress sensor IRE1α as a critical checkpoint that restricts the immunostimulatory effects of taxane chemotherapy and prevents the innate immune recognition of immunologically cold triple-negative breast cancer (TNBC). IRE1α RNase silences taxane-induced double-stranded RNA (dsRNA) through regulated IRE1-dependent decay (RIDD) to prevent NLRP3 inflammasome-dependent pyroptosis. Inhibition of IRE1α in Trp53^-/- TNBC allows taxane to induce extensive dsRNAs

SUBMITTER: Xu L 

PROVIDER: S-EPMC11645245 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature