Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Immunol. 2021 Apr 15;12:657575. doi: 10.3389/fimmu.2021.657575. eCollection 2021.
Immune checkpoint blockade (ICB) therapies have significantly improved the prognosis and shown considerable promise for cancer therapy; however, differences in ICB treatment efficacy between the elderly and young are unknown. We analyzed the studies enrolled in the meta-analysis using the deft approach, and found no difference in efficacy except melanoma patients receiving anti-PD-1 therapy. Similarly, higher treatment response rate and more favorable prognosis were observed in elderly patients in some cancer types (e.g., melanoma) with data from published ICB treatment clinical trials. In addition, we comprehensively compared immunotherapy-related molecular profiles between elderly and young patients from public trials and The Cancer Genome Atlas (TCGA), and validated these findings in several independent datasets. We discovered a divergent age-biased immune profiling, including the properties of tumors (e.g., tumor mutation load) and immune features (e.g., immune cells), in a pancancer setting across 27 cancer types. We believe that ICB treatment efficacy might vary depending on specific cancer types and be determined by both the tumor internal features and external immune microenvironment. Considering the high mutational properties in elderly patients in many cancer types, modulating immune function could be beneficial to immunotherapy in the elderly, which requires further investigation.
免疫检查点阻断 (ICB) 疗法显著改善了预后，并为癌症治疗带来了巨大的希望；然而，老年人和年轻人之间 ICB 治疗效果的差异尚不清楚。我们使用 deft 方法分析了纳入荟萃分析的研究，结果发现除了接受抗 PD-1 治疗的黑色素瘤患者外，疗效没有差异。同样，在一些癌症类型（如黑色素瘤）中，来自发表的 ICB 治疗临床试验的数据显示，老年患者的治疗反应率更高，预后更好。此外，我们全面比较了来自公共试验和癌症基因组图谱 (TCGA) 的老年和年轻患者的免疫治疗相关分子谱，并在几个独立数据集验证了这些发现。我们发现，在 27 种癌症类型的泛癌环境中，存在一种不同的年龄偏倚免疫特征，包括肿瘤的特性（如肿瘤突变负荷）和免疫特征（如免疫细胞）。我们认为，ICB 治疗效果可能因特定癌症类型而异，并由肿瘤内部特征和外部免疫微环境决定。考虑到许多癌症类型中老年人的高突变特性，调节免疫功能可能对老年人的免疫治疗有益，这需要进一步研究。
