在微卫星稳定的结直肠癌中,在向治疗后获得的高瘤突变负担和免疫疗法的活性
Celine Yeh1, Oliver Artz2, Haochen Zhang3
1Memorial Sloan Kettering Cancer Center, New York, NY, United States.
概括
向治疗可以增加微卫星稳定 (MSS) 大肠直肠癌 (CRCs) 的瘤突变负担 (TMB). 然而,这种获得的TMB并没有使MSSCRC对免疫检查点封锁 (ICB) 敏感.
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:
- 微卫星稳定 (MSS) 大肠直肠癌 (CRCs) 由于瘤突变负担 (TMB) 较低,通常对免疫检查点阻塞 (ICB) 不敏感.
- 向治疗可以在治疗进展过程中诱导CRC的基因组变化.
研究的目的:
- 调查是否有针对性的治疗可以增加MSSCRC中的TMB.
- 为了确定是否获得的高TMB使MSSCRC对ICB敏感.
主要方法:
- 评估基线和进展TMB在MSS转移性CRC患者治疗有针对性的治疗.
- 在获得高TMB的患者中评估ICB反应.
- 在获得高TMB的病例中分析基因组变化,突变特征,新抗原性和克隆性.
主要成果:
- 在26例MSSCRC病例中,9例在向治疗后获得了高TMB.
- 接受ICB的三名获得高TMB的患者没有反应.
- 获得的高TMB是由亚克隆性改变驱动的,缺乏免疫细胞透,并且没有增强免疫识别.
结论:
- 向治疗可以导致MSSCRC的显著比例获得高TMB.
- 在MSS CRC中获得的高TMB并不能转化为对ICB的敏感性.
- 驱动TMB的亚克隆基因组变化不足以诱导显著的抗瘤免疫反应.
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