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RPTOR突变:在黑色素瘤中有效免疫治疗的新型预测因素
Yanfang Jiang1, Xintong Hu1, Zhouyu Wang2
1Genetic Diagnosis Center, The First Hospital of Jilin University, Changchun, 130021, China.
Investigational new drugs
|December 10, 2023
概括
调控相关蛋白的MTOR复合体1 (RPTOR) 突变预测黑色素瘤患者治疗免疫检查点抑制剂 (ICI) 的更好的结果. RPTOR突变与改善的生存率和响应率有关,这表明它们作为预测生物标志物的潜力.
科学领域:
- 在瘤学瘤学.
- 免疫治疗是一种免疫疗法.
- 基因组学就是基因组学.
背景情况:
- 确定免疫检查点抑制剂 (ICI) 在黑色素瘤中有效性的生物标志物至关重要.
- 在黑色素瘤免疫疗法反应中,MTOR复合体1 (RPTOR) 突变调控相关蛋白的作用尚不清楚.
研究的目的:
- 研究RPTOR突变与ICI在黑色素瘤患者中的疗效之间的关联.
- 探索连接RPTOR突变与免疫疗法反应的潜在机制.
主要方法:
- 利用来自cBioPortal的ICI治疗黑色素瘤患者的发现 (n=384) 和验证 (n=320) 队列的基因组数据.
- 分析了癌症基因组图谱 (TCGA) -皮肤皮肤黑色素瘤 (SKCM) 队列,以获得机械的见解.
- 评估的整体存活率 (OS),客观反应率 (ORR),瘤突变负担 (TMB),DNA损伤反应 (DDR) 突变,免疫细胞透和与免疫相关的基因表达.
主要成果:
- 与RPTOR野生型 (RPTOR-WT) 患者相比,RPTOR突变 (RPTOR-Mut) 黑色素瘤患者在两个队列中都显示出明显延长的OS.
- 与RPTOR-WT患者相比,RPTOR-Mut患者的ORR和TMB均高于RPTOR-WT患者.
- RPTOR-Mut瘤呈现出增加的DDR突变,激活的CD4记忆T细胞的丰富,以及更高的免疫相关基因表达.
结论:
- RPTOR突变状态是黑色素瘤有效免疫治疗的潜在预测生物标志物.
- RPTOR突变与有利的临床结果和炎症瘤微环境有关,以应对ICI.
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