随着年龄的增长，适应性免疫系统逐渐衰退，同时癌症发病率急剧上升。在这项研究中，我们着手了解高龄抗肿瘤免疫缺陷是否会促进肿瘤进展和/或导致对免疫治疗的耐药性。我们发现，由于 CD8 T 细胞反应功能失调，老年小鼠的多种同基因癌症比年轻的成年小鼠生长得更快。通过系统地绘制肿瘤内的免疫细胞图谱，我们发现肿瘤抗原特异性 CD8 T 细胞的丧失是加速老年小鼠肿瘤生长并导致对免疫治疗产生耐药性的主要特征。当将来自年轻成年小鼠的抗原特异性 T 细胞给予老年小鼠时，肿瘤的生长被延迟，并且老年动物对 PD-1 阻断变得敏感。这些研究揭示了与年龄相关的 CD8 T 细胞功能障碍如何允许老年患者发生肿瘤，并对使用老年小鼠作为衰老和癌症的临床前模型具有重要意义。

Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses. By systematically mapping immune cell profiles within tumors, we identified loss of tumor antigen-specific CD8+ T cells as a primary feature accelerating the growth of tumors in aged mice and driving resistance to immunotherapy. When antigen-specific T cells from young adult mice were administered to aged mice, tumor outgrowth was delayed and the aged animals became sensitive to PD-1 blockade. These studies reveal how age-associated CD8+ T-cell dysfunction may license tumorigenesis in elderly patients and have important implications for the use of aged mice as pre-clinical models of aging and cancer.