Aging is one of the biggest risk factors for cancer development. Over 85% of all cancers occur in individuals aged over 55 years, often accompanied by age-associated immune defects. Previous studies on the tumor microenvironment (TME) during aging have identified several factors, such as the roles of fibroblasts, immunosuppression, and metastasis. However, the aging-associated defects in anti-tumor immunity, particularly regarding T cells, remain underexplored. Recent findings by Zhivaki and colleagues suggest that age-related immune defects affecting anti-tumor responses involve reduced levels of CD8+ T cells and compromised dendritic cell (DC) functions such as antigen presentation and migration. Their study demonstrates that a hyperactive DC vaccine can restore DC functions in older mice. Furthermore, these hyperactive DCs, characterized by increased IL-1β production and better migratory capability to the lymph node, promote the development of cytolytic CD4+ T cells exhibiting Th1-like phenotypes. This research reveals mechanisms underlying the response to hyperactive DC vaccines in older mice and highlights the critical role of cytolytic CD4+ T cells as substitutes for CD8+ T cells in driving anti-tumor immunity and achieving long-term tumor control in older mice.

中文翻译：

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过度活跃的 DC 重定向老化的抗肿瘤免疫力


衰老是癌症发展的最大风险因素之一。超过 85% 的癌症发生在 55 岁以上的个体中，通常伴有与年龄相关的免疫缺陷。先前对衰老过程中肿瘤微环境 （TME） 的研究已经确定了几个因素，例如成纤维细胞的作用、免疫抑制和转移。然而，抗肿瘤免疫的衰老相关缺陷，尤其是 T 细胞，仍未得到充分探索。Zhivaki 及其同事最近的研究结果表明，影响抗肿瘤反应的年龄相关免疫缺陷涉及 CD8+ T 细胞水平降低和树突状细胞 （DC） 功能受损，例如抗原呈递和迁移。他们的研究表明，过度活跃的 DC 疫苗可以恢复老年小鼠的 DC 功能。此外，这些过度活跃的 DC 以 IL-1β 产生增加和更好的向淋巴结迁移能力为特征，促进表现出 Th1 样表型的溶细胞 CD4+ T 细胞的发育。这项研究揭示了老年小鼠对过度活跃的 DC 疫苗反应的潜在机制，并强调了溶细胞 CD4+ T 细胞作为 CD8+ T 细胞替代品在驱动抗肿瘤免疫和实现老年小鼠长期肿瘤控制方面的关键作用。