与PD-L1表达相关的PI3K通路与免疫治疗在胃癌中的疗效相关
Langbiao Liu1, Lei Niu1, Xue Zheng2
1Beijing Key Laboratory of Cancer Invasion and Metastasis Research & National Clinical Research Center for Digestive Diseases, Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Therapeutic advances in medical oncology
|October 23, 2023
概括
编程死亡配体1 (PD-L1) 综合阳性得分 (CPS) 预测胃癌的免疫治疗反应. PI3K路径的改变与PD-L1阳性和改善免疫治疗结果相关,有助于患者选择.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 免疫治疗是一种免疫疗法.
背景情况:
- 编程死亡连接体1 (PD-L1) 综合阳性评分 (CPS) 是FDA批准的胃癌 (GC) 免疫疗法的生物标志物,但不完美.
- 了解影响PD-L1 CPS的分子因素对于确定能从免疫疗法中受益的患者至关重要.
研究的目的:
- 调查与胃癌中PD-L1表达相关的分子特征.
- 确定这些分子变化是否与免疫疗法疗效相关.
主要方法:
- 在492名GC患者中使用PD-L1免疫组织化学 (IHC) 和下一代测序.
- 在PD-L1阳性 (CPS ≥1) 和阴性 (CPS <1) 组之间比较了基因组变化.
- 在三个独立的GC队列中分析了免疫疗法的疗效.
主要成果:
- 在40%的GC患者中观察到PD-L1阳性.
- PD-L1表达与酸丁3-激酶 (PI3K),SWI/SNF,氨酸脱甲基酶 (KDM) 和DNA甲基转移酶 (DNMT) 途径的改变有关 (p <0.01).
- 与野生型相比,患有PI3K通路改变的患者显示出显著更高的应答率,持久的临床益处和免疫疗法改善的生存率.
结论:
- 这项研究确定了胃癌中与PD-L1表达相关的基因组因素.
- 与PD-L1阳性相关的PI3K路径改变预测了更好的免疫治疗反应.
- 这些发现为改善GC患者选择和组合疗法开发提供了基础.
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