Immunogenic PANoptosis-Initiated Cancer Sono-Immune Reediting Nanotherapy by Iteratively Boosting Cancer Immunity Cycle

The cancer-immune cycle conceptualized the mechanisms of driving T cell responses to tumors, but w as limited by immunological ignorance elicited by tumor inherent immunoediting, which failed to initiate and maintain adaptive immunity. Targeting specific vulnerabilities of cell death patterns may provide unique opportunities to boost T cell antitumor immunological effects. Here an ultrasound nanomedicine-triggered tumor immuno-reediting therapeutic strategy using nano/genetically engineered extracellular vesicles, which can induce tumor highly immunogenic PANoptosis and iteratively start-up the energization of cancer innate immunity cycle by repeatedly liberating damage-associated molecular patterns, thereby priming sufficient antigen-specific T cells and shaping protective immune response through activating cGAS-STING signaling pathways, is reported. Aided by immune checkpoint blockade, the reprogramming of immune microenvironment further facilitated a prompt bridging of innate and adaptive immunity, and remarkably suppressed metastatic and rechallenged tumor growth. Thus, targeting PANoptotic cell death provides a catcher against immune escape and a positive-feedback immune activation gateway for overcoming immune resistance to intractable cancers. A nano/genetically engineered sonosensitive extracellular vesicles are rationally designed for ultrasound nanomedicine-triggered tumor immuno-reediting therapeutic by efficiently inducing tumor immunogenic PANoptosis and iteratively boosting cancer innate immunity cycle. This specific regulated cell death renders tumor cells highly immunogenic through maximally activating damage-associated molecular patterns, thereby reprogramming negative immune microenvironment and advancing positive adaptive antitumor immune response.image

Automated summary

This article introduces a therapeutic strategy for tumor immune re-editing triggered by ultrasound nanomedicine, which enhances the immune response to tumors by releasing damage-associated molecular patterns, thereby improving the effectiveness of T cells in fighting cancer.