Dolan Melissa, Libby Kendra A, Ringel Alison E, van Galen Peter, McAllister Sandra S
Hematology Division, Department of Medicine, Brigham & Women's Hospital, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Nat Rev Cancer. 2025 Aug 14. doi: 10.1038/s41568-025-00858-z.
The immune system undergoes substantial changes throughout life, with ageing broadly impacting immune cell composition, function and regenerative capacity. Emerging evidence suggests that age-associated changes in immune fitness - the ability to respond to and eliminate infection, pathogens and malignancy while maintaining self-tolerance - reshape antitumour immunity and influence the efficacy of immunotherapies. Technological advances in high-dimensional immunoprofiling have begun to reveal the complex interplay between ageing, immune fitness and cancer biology, uncovering new therapeutic vulnerabilities and challenges. In this Review, we discuss recent insights derived from age-resolved immunoprofiling of the human tumour microenvironment, how ageing haematopoiesis affects immune cells that contribute to the microenvironment and impact cancer progression, and what is known from preclinical modelling about the functional consequences of immune ageing on tumour control. We further highlight emerging age-stratified analyses of treatment responses, which are beginning to inform hypotheses about how ageing shapes immunotherapy outcomes. Together, these perspectives provide a framework for integrating age as a critical biological variable, underscore the need to consider age in both preclinical models and clinical trial design, and identify key challenges and priorities for the field moving forward.
免疫系统在整个生命过程中会发生重大变化,衰老会广泛影响免疫细胞的组成、功能和再生能力。新出现的证据表明,免疫适应性(即在维持自身耐受性的同时对感染、病原体和恶性肿瘤作出反应并将其清除的能力)与年龄相关的变化会重塑抗肿瘤免疫力,并影响免疫疗法的疗效。高维免疫分析技术的进步已开始揭示衰老、免疫适应性和癌症生物学之间的复杂相互作用,发现新的治疗弱点和挑战。在本综述中,我们讨论了从对人类肿瘤微环境进行年龄解析的免疫分析中获得的最新见解,衰老的造血过程如何影响有助于微环境并影响癌症进展的免疫细胞,以及临床前模型中关于免疫衰老对肿瘤控制的功能后果的已知情况。我们还强调了新兴的年龄分层治疗反应分析,这些分析开始为衰老如何塑造免疫治疗结果的假说提供依据。总之,这些观点提供了一个将年龄作为关键生物学变量进行整合的框架,强调了在临床前模型和临床试验设计中考虑年龄的必要性,并确定了该领域未来发展的关键挑战和优先事项。
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