老年人的分化型甲状腺癌与突变景观和肿瘤免疫细胞浸润的改变有关，从而创造了肿瘤允许的微环境。我们试图确定年龄对甲状腺乳头状癌 (PTC) 基因组改变和免疫细胞组成的影响。使用癌症基因组图谱 (TCGA) 和计算免疫基因组分析获得基因组改变、免疫细胞组成和临床数据。疾病严重程度被重新编码为 3 组：A 组（T1-2N0M0）、B 组（T1-3N1a-1bM0）和 C 组（T4NxMx 或 TxNxM1）。组织病理学亚型包括常规 PTC、滤泡变异型和高细胞变异型 PTC。进行了斯皮尔曼等级相关、方差分析、t 检验和多元线性回归。从 TCGA 门户检索了 470 个 PTC 样本，其中包含基因组改变和免疫细胞组成数据。 TERT 启动子改变在 ≥ 65 岁的患者中更为常见（26% vs 4%，p<0.0001）。肿瘤突变负荷随着年龄的增加而增加（r=0.463，p<0.0001）。使用 CIBERSORT 时，年龄增长与 CD8 T 细胞减少 (r=-0.15，p=0.01) 以及 B 细胞 (r=-0.13)、CD8 T 细胞 (r=-0.19) 和中性粒细胞 (r=-0.14，p) 减少相关<0.05) 使用定时器。多变量回归发现，年龄的增加与静息 NK 细胞和静息树突状细胞的增加以及幼稚 B 细胞和 CD8 T 细胞的减少独立相关 (p<0.05)。老年人 PTC 肿瘤的特点是 TERT 启动子改变增加、肿瘤突变负荷增加、细胞毒性 CD8 T 减少和静息树突细胞免疫浸润增加。需要进一步的研究来确定免疫细胞浸润的这些变化是否与结果受损有关。

Differentiated thyroid cancer in older adults has been linked to alterations in the mutational landscape and tumor immune cell infiltration that create a tumor-permissive microenvironment. We sought to determine the impact of age on genomic alterations and immune cell composition in papillary thyroid cancer (PTC). Genomic alterations, immune cell composition and clinical data were obtained using The Cancer Genome Atlas (TCGA) and computational immunogenomic analyses. Disease severity was recoded into 3 groups: Group A (T1-2N0M0), Group B (T1-3N1a-1bM0), and Group C (T4NxMx or TxNxM1). Histopathologic subtypes included conventional, follicular-variant, and tall cell variant PTC. Spearman's rank correlation, ANOVA, t-test, and multivariable linear regression were performed. 470 PTC samples were retrieved from the TCGA portal with genomic alteration and immune cell composition data. TERT promoter alterations were more common in patients ≥ 65 years (26% vs 4%, p<0.0001). Tumor mutational burden increased with increasing age (r=0.463, p<0.0001). Increasing age was associated with decreased CD8+ T cells (r=-0.15, p=0.01) using CIBERSORT and decreased B cells (r=-0.13), CD8+ T cells (r=-0.19) and neutrophils (r=-0.14, p<0.05) using TIMER. Multivariate regression found that increasing age was independently associated with increased resting NK cells and resting dendritic cells, and decreased naïve B cells and CD8+ T cells (p<0.05). PTC tumors of older adults are characterized by increased TERT promoter alterations, increased tumor mutational burden, and a decreased cytotoxic CD8+ T and increased resting dendritic cell immune infiltrate. Further studies are needed to determine if these changes in immune cell infiltrate are associated with compromised outcomes.