编辑丨王多鱼 排版丨水成文 时间永不停歇地前进……但这对于免疫系统意味着什么？ 近期， Immunity 期刊 特邀来自中国科学院 （ 刘光慧 、 田烨 ） 、斯坦福大学、剑桥大学等机构的一组知名学者， 围绕衰老如何影响免疫反应、免疫细胞如何 参与衰老进程等关键问题展开了深入探讨。这些讨论为 通过调控免疫力以延长健康寿命 提供了新的科学视角。 Christoph A. Thaiss ， Arc 研究所，斯坦福大学， 感知免疫变化 在其 1956 年前瞻性讲座《 心灵与物质 》的开篇，物理学家 埃尔温 · 薛定谔 指出： " 世界是我们感觉、知觉与记忆的建构产物。 " 这一建构基于两大感觉系 统：外感受负责感知外部物理与化学环境，内感受则负责感知机体内在环境。免疫细胞发出的信号极大地拓展了内感受的疆界 —— 例如，响应微生物识别而释放 的细胞因子可激活感觉神经元上的受体，进而将信号传递至大脑，协调适应性反应。 尽管外感受功能随年龄增长而衰退 （日常生活中常通过眼镜或助听器等设备进行补偿） ，但关于内感受如何衰老，我们仍知之甚少。免疫细胞功能在整个生命周 期中发生深刻变化：骨髓造血输出呈现髓系偏倚，记忆性 T 细 ...

Core Viewpoint - The research highlights the role of dietary flavonoid quercetin and its microbial metabolite DOPAC in enhancing CD8⁺ T cell anti-tumor immunity, suggesting DOPAC as a potential candidate for cancer immunotherapy [2][8]. Group 1: Mechanism of Action - Quercetin, when metabolized by gut microbiota, produces DOPAC, which enhances CD8⁺ T cell anti-tumor immunity through NRF2-mediated mitophagy [3][4]. - DOPAC binds directly to KEAP1 protein, disrupting its interaction with NRF2, thereby preventing KEAP1-mediated NRF2 degradation [4]. - Increased NRF2 activity leads to enhanced transcription of BNIP3, promoting mitophagy and improving the adaptability of CD8⁺ T cells in the tumor microenvironment [4][6]. Group 2: Synergistic Effects - DOPAC exhibits a synergistic effect with immune checkpoint blockade (ICB) therapy, further inhibiting tumor growth [5][6]. Group 3: Implications for Cancer Treatment - The findings underscore the importance of dietary nutrients and their microbial metabolites in regulating anti-tumor immune responses, positioning DOPAC as a promising candidate for cancer immunotherapy [8].

Core Viewpoint - The study reveals the critical role of immature neutrophils in the bone metastatic microenvironment and suggests a potential therapeutic strategy to improve cancer immunotherapy by regulating these cells [3][7]. Group 1: Research Findings - Immature neutrophils dominate the bone metastatic microenvironment in both mouse models and cancer patients [5]. - DKK1 induces neutrophils to exhibit an immature functional state, which possesses strong immunosuppressive capabilities, inhibiting CD8+ T cell anti-tumor responses [5]. - The DKK1-CKAP4-STAT6 signaling pathway drives CHI3L3 expression, essential for the immunosuppressive role of immature neutrophils in bone metastases [5]. Group 2: Therapeutic Implications - Blocking DKK1 can promote neutrophil maturation, improve the immune microenvironment, induce tumor shrinkage, and enhance responses to immune checkpoint blockade therapy [3][5]. - The findings propose a promising new strategy for combined immunotherapy targeting bone metastases by modulating neutrophil activity [7].