癌症免疫周期概念化了推动T细胞对肿瘤产生反应的机制，但受到了肿瘤天生免疫编辑所诱发的免疫忽视的限制，未能启动和保持适应性免疫。针对细胞死亡模式的特定脆弱性可能提供增强T细胞抗肿瘤免疫效应的独特机会。在这里，我们报告了一种超声纳米医学触发的肿瘤免疫重编程治疗策略，使用纳米/基因工程外泌体能诱导肿瘤高度免疫原性的全面细胞死亡，并通过反复释放与损伤相关的分子模式来迭代启动癌症固有免疫周期的激活，从而引发足够数量的抗原特异性T细胞并通过激活cGAS-STING信号通路来塑造保护性免疫应答。借助免疫检查点阻断的帮助，免疫微环境的重编程进一步促进了先天免疫和适应性免疫的及时连接，并显著抑制了转移和再挑战的肿瘤生长。因此，靶向全面细胞死亡为免疫逃逸提供了一种捕获机制，为克服难治性癌症的免疫抵抗提供了正反馈的免疫激活通道。版权所有，禁止转载。

The cancer-immune cycle conceptualized the mechanisms of driving T cell responses to tumors, but was 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 anti-tumor immunological effects. Here we report 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. 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. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.