A range of advanced nanovaccines (NV) combined with immunotherapies has recently emerged for treating malignant tumors and has demonstrated promising tumor-suppressive effects. Nevertheless, their effectiveness is often limited by immunosuppression within the tumor microenvironment. To overcome this challenge, new approaches for NV development are required to improve antigen cross-presentation and to remodel the tumor microenvironment. In this issue of Cancer Research, Zhou and colleagues have developed a photo-enhanceable inflammasome-activating nanovaccine (PIN) designed for precise, in situ delivery of a tumor antigen and a hydrophobic small molecule that activates the NLRP3 inflammasome pathway. Near infrared light exposure enables the accumulation of PINs at tumor sites by inducing a photo-triggered charge reversal in the BODIPY-modified PAMAM nanocarrier. Systemic administration of PINs resulted in effective intratumoral activation of the NLRP3 inflammasome and antigen cross-presentation in antigen-presenting cells upon light exposure, leading to enhanced immune responses through increased proinflammatory cytokine production without significant systemic toxicity. Importantly, PINs also enhanced the efficacy of immune checkpoint blockade and promoted the development of long-term immune memory in mouse models of melanoma and hepatocellular carcinoma. Overall, inflammasome-activating NVs represent a cancer immunotherapy strategy by harnessing the innate immune system to achieve robust responses against tumors. Ongoing research and development are crucial to addressing current limitations and advancing this innovative technology toward clinical application. See related article by Zhou et al., p. 3834

中文翻译：

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用于癌症免疫治疗的炎性小体激活纳米疫苗


最近出现了一系列先进的纳米疫苗 （NV） 联合免疫疗法用于治疗恶性肿瘤，并显示出良好的肿瘤抑制作用。然而，它们的有效性通常受到肿瘤微环境中免疫抑制的限制。为了克服这一挑战，需要新的 NV 开发方法来改善抗原交叉呈递并重塑肿瘤微环境。在本期《癌症研究》中，周及其同事开发了一种光增强的炎性小体激活纳米疫苗（PIN），旨在精确、原位递送肿瘤抗原和激活NLRP3炎性小体通路的疏水小分子。近红外光暴露通过在 BODIPY 修饰的 PAMAM 纳米载体中诱导光触发电荷反转，使 PIN 在肿瘤部位积累。PINs 的全身给药导致 NLRP3 炎性小体的有效瘤内激活和光照后抗原呈递细胞中的抗原交叉呈递，通过增加促炎细胞因子的产生而增强免疫反应，而没有明显的全身毒性。重要的是，PINs 还增强了免疫检查点阻断的功效，并促进了黑色素瘤和肝细胞癌小鼠模型中长期免疫记忆的发育。总体而言，炎性小体激活 NV 代表了一种癌症免疫治疗策略，它利用先天免疫系统实现对肿瘤的稳健反应。持续的研究和开发对于解决当前限制并将这项创新技术推向临床应用至关重要。参见 周 et al. 的相关文章，第 3834 页