先天性和适应性免疫对于启动和维持免疫功能很重要。核苷酸结合寡聚化结构域样受体家族含pyrin结构域3 (NLRP3)炎症小体作为先天性和适应性免疫的检查点，促进促炎细胞因子的分泌和gasdermin D介导的细胞焦亡。作为一种与细胞凋亡不同的高度炎症性细胞死亡形式，细胞焦亡可以触发免疫原性细胞死亡并促进实体瘤中的全身免疫反应。先前的研究提出，NLRP3 通过易位至线粒体而被激活。然而，最近的一项权威研究对这一模型提出了挑战，并证明高尔基体可能是NLRP3激活的先决条件。在这项研究中，我们首先开发了一种高尔基体靶向光动力策略，通过精确定位细胞器来诱导 NLRP3 的激活。我们发现高尔基体靶向光动力疗法可以显着上调NLRP3的表达，促进细胞内促炎成分如IL-1β或IL-18的释放，形成炎症风暴，增强先天免疫。此外，这种急性NLRP3上调还激活了其下游经典的caspase-1依赖性细胞焦亡，以增强肿瘤免疫原性，引发适应性免疫。细胞焦亡最终导致免疫原性细胞死亡，促进树突状细胞成熟，有效激活抗肿瘤免疫和长效免疫记忆。总体而言，这种高尔基体靶向策略提供了对免疫原性细胞焦亡发生的分子见解，并提供了重塑肿瘤微环境的平台。

Innate and adaptive immunity is important for initiating and maintaining immune function. The nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome serves as a checkpoint in innate and adaptive immunity, promoting the secretion of pro-inflammatory cytokines and gasdermin D-mediated pyroptosis. As a highly inflammatory form of cell death distinct from apoptosis, pyroptosis can trigger immunogenic cell death and promote systemic immune responses in solid tumors. Previous studies proposed that NLRP3 was activated by translocation to the mitochondria. However, a recent authoritative study has challenged this model and proved that the Golgi apparatus might be a prerequisite for the activation of NLRP3. In this study, we first developed a Golgi apparatus-targeted photodynamic strategy to induce the activation of NLRP3 by precisely locating organelles. We found that Golgi apparatus-targeted photodynamic therapy could significantly upregulate NLRP3 expression to promote the subsequent release of intracellular proinflammatory contents such as IL-1β or IL-18, creating an inflammatory storm to enhance innate immunity. Moreover, this acute NLRP3 upregulation also activated its downstream classical caspase-1-dependent pyroptosis to enhance tumor immunogenicity, triggering adaptive immunity. Pyroptosis eventually led to immunogenic cell death, promoted the maturation of dendritic cells, and effectively activated antitumor immunity and long-lived immune memory. Overall, this Golgi apparatus-targeted strategy provided molecular insights into the occurrence of immunogenic pyroptosis and offered a platform to remodel the tumor microenvironment.