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 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 尿石素 A （Urolithin A，UA） 是由富含 鞣花单宁 （例如 石榴 、树莓等） 的食物在肠道菌群中代谢产生 的化合物，可以激活线粒体自噬，改善线粒体健康。 2022 年 10 月，德国法兰克福大学医院 Florian Greten 团队 在 Immunity 期刊发表论文 【1】 。该研究显 示， 尿石素 A （UA） 能够通过 激活线粒体自噬 ，促进 T 记忆干细胞 （T scm ） 扩增，为免疫系统提供 恢复活力、不耗竭的 T 细胞， 从而通过直接调控免疫系统来抑制癌症生长。 2025 年 10 月 31 日， Florian Greten 团队在 Nature Aging 期刊发表了题为： Effect of the mitophagy inducer urolithin A on age-related immune decline: a randomized, placebo-controlled trial 的研究论 文。 这项 随机、双盲、安慰剂对照的临床试验表明，短期 （4 周） 口服 尿石素 A （每天 1000 毫克） ， 可 调控人体免 ...

Core Insights - The article discusses the advancements in cancer immunotherapy and highlights the challenge of low response rates, with less than 20% of cancer patients achieving durable responses to immunotherapy [2] - It emphasizes the role of immune senescence in tumor microenvironments as a key factor leading to resistance to immunotherapy, suggesting that targeting immune aging could enhance treatment efficacy [3][9] Group 1: Research Findings - A recent study published in Nature Medicine confirmed that immune senescence in the tumor microenvironment is a critical factor for immunotherapy resistance, demonstrating that senolytic drugs combined with anti-PD-1 therapy significantly improved response rates in head and neck squamous cell carcinoma (HNSCC) patients [3][6] - The study involved a Phase 2 clinical trial with 51 patients, revealing that treatment-related adverse reactions were associated with decreased levels of CCR7+ CD4+ naive T cells and CD27+ memory B cells, alongside high expression of immune senescence-related genes [6][7] Group 2: Clinical Trial Results - The first global Phase 2 clinical trial combining senolytic drugs with anti-PD-1 therapy showed a major pathological response rate of 33.3%, including a complete pathological response rate of 16.7%, significantly outperforming historical data for monotherapy [7] - The incidence of grade 3-4 adverse events was low at 4.2%, much lower than the 51% seen with chemotherapy combined with immunotherapy, indicating a favorable safety profile for the combination treatment [7] Group 3: Implications for Future Research - The findings provide valuable insights into the variability of tumor immune microenvironments and highlight the potential of targeting immune senescence to enhance anti-tumor efficacy [9] - The COIS-01 trial opens new avenues for combining immunotherapy with anti-aging strategies in the treatment of solid tumors, suggesting that enhancing immunity while reducing or reversing immune aging is a promising area for further exploration [9]