免疫肿瘤学 (IO) 研究很大程度上依赖于小鼠同基因肿瘤模型。然而，虽然癌症诊断的平均年龄为 60 岁或以上，但出于实际目的，大多数临床前研究都是在年轻小鼠中进行的，尽管事实证明衰老对免疫反应有显着影响。 （60-72周龄）携带CT26肿瘤的小鼠，我们研究了衰老对肿瘤生长以及肿瘤和外周淋巴器官的免疫组成的影响。我们发现肿瘤和肿瘤的免疫细胞组成有很多差异- 老年小鼠和年轻小鼠之间的淋巴结引流，例如老年动物中幼稚 T 细胞数量的减少和瘤内 CD8/Treg 比率的降低。我们假设这些差异可能导致老年小鼠抗癌免疫反应受损，因此评估了老年小鼠中不同 IO 疗法的抗肿瘤功效，包括共刺激（使用抗 OX40 抗体）和免疫检查点阻断（使用抗 PD-L1 和抗 CTLA-4 抗体）。虽然老年小鼠保留了产生抗肿瘤免疫反应的能力，但与年轻小鼠中观察到的反应相比，这些反应显着减弱。这些差异凸显了年龄相关的免疫学变化在评估和完善从临床前小鼠获得的转化见解方面的重要性模型。版权所有 © 2023 Sitnikova、Walker、Prickett、Morrow、Valge-Archer、Robinson、Wilkinson 和 Dovedi。

Immuno-oncology (IO) research relies heavily on murine syngeneic tumor models. However, whilst the average age for a cancer diagnosis is 60 years or older, for practical purposes the majority of preclinical studies are conducted in young mice, despite the fact that ageing has been shown to have a significant impact on the immune response.Using aged (60-72 weeks old) mice bearing CT26 tumors, we investigated the impact of ageing on tumor growth as well as the immune composition of the tumor and peripheral lymphoid organs.We found many differences in the immune cell composition of both the tumor and tumor-draining lymph node between aged and young mice, such as a reduction in the naïve T cell population and a decreased intratumoral CD8/Treg ratio in aged animals. We hypothesized that these differences may contribute to impaired anti-cancer immune responses in aged mice and therefore assessed the anti-tumor efficacy of different IO therapies in aged mice, including both co-stimulation (using an anti-OX40 antibody) and immune checkpoint blockade (using anti-PD-L1 and anti-CTLA-4 antibodies). Whilst aged mice retained the capacity to generate anti-tumor immune responses, these were significantly attenuated when compared to the responses observed in young mice.These differences highlight the importance of age-related immunological changes in assessing and refining the translational insights gained from preclinical mouse models.Copyright © 2023 Sitnikova, Walker, Prickett, Morrow, Valge-Archer, Robinson, Wilkinson and Dovedi.