PAPPA2突变重构炎性肿瘤微环境促进免疫检查点抑制剂治疗应答

PAPPA2 mutation reconstructs inflamed tumor microenvironment and promotes responsiveness to immune checkpoint inhibitor

目的研究实体肿瘤中PAPPA2突变肿瘤免疫微环境特征及其与免疫检查点抑制剂治疗应答的相关性。方法8 887例实体瘤患者的全外显子组测序数据、表达谱数据及临床随访数据从TCGA数据库下载得到,不同实体瘤对免疫检查点抑制剂的客观缓解率由文献报道中获得。结果表达谱数据分析发现PAPPA2突变型患者具有更高的IFNG、STAT1等T细胞应答相关分子表达,且趋化因子-细胞因子相关信号通路活化。进一步临床数据分析发现不同瘤种中PAPPA2突变的发生率与其对免疫检查点抑制剂治疗的客观缓解率呈显著正相关。结论研究提示PAPPA2突变可能作为免疫检查点抑制剂治疗应答的预测生物标志物。在临床实践中进一步验证后,可为患者实施精准免疫治疗提供参考依据。

This study was performed to validate the predictive value of PAPPA2 mutations in the response to immunotherapy and to survey its immunological relevance in solid tumors.Whole exome sequencing data,expression profiles,and clinical characteristics of 8 887 patients with solid tumor were retrieved from The Cancer Genome Atlas database.Data showed that the levels of T-cell-inflamed immune-related genes were higher in PAPPA2 mutation carriers than those in wild-type PAPPA2 carriers.Furthermore,the frequencies of PAPPA2 mutation is positively associated with the objective response rate to immune checkpoint inhibitors across multiple solid tumor types.In conclusion,PAPPA2 mutation is a promising predictive biomarker for the identification of patient subsets likely to respond to immune checkpoint blockade in clinical practice.