在结直肠癌中AXL的临床和分子表征,CALGB (联盟) /SWOG 80405和现实世界的数据
Karam Ashouri1, Joshua Millstein2, Yan Yang2
1Division of Medical Oncology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California, USA.
Journal for immunotherapy of cancer
|December 21, 2025
概括
大肠直肠癌 (CRC) 中高AXL表达表明免疫抑制瘤微环境和标准治疗的较差结果. 然而,它确定了从免疫治疗中显著受益的KRAS突变患者.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- AXL受体氨酸激酶失调与瘤耐药性和免疫微环境调节有关.
- 识别那些将受益于AXL向治疗的患者仍然是结直肠癌 (CRC) 的挑战.
- 这项研究描述了AXL在CRC临床和分子环境中的作用.
研究的目的:
- 调查在结直肠癌 (CRC) 中AXL表达的临床和分子意义.
- 确定AXL表达,免疫微环境和患者结果之间的关联.
- 评估AXL作为CRC治疗反应的预测生物标志物.
主要方法:
- 集成的真实世界的分子分析数据 (n=24,257) 和一个随机临床试验 (CALGB/SWOG 80405;n=433) 对于CRC患者.
- 通过RNA测序评估了AXL信使RNA (mRNA) 表达,并分析了瘤免疫微环境.
- 利用Kaplan-Meier和Cox的比例危险模型来评估AXL表达,分子特征,免疫生物标志物和临床结果 (整体生存[OS],无进展生存[PFS]) 之间的关联.
主要成果:
- 增加的AXL表达与增加的PD-L1阳性,免疫检查点基因表达和免疫抑制细胞透 (T调节细胞,M2巨细胞,单细胞,B细胞) 相关联.
- 高AXL表达与上皮细胞-介质细胞过渡和炎症信号通路有关.
- 在Caris队列中,高AXL预测了标准化疗,贝瓦齐祖马布和抗EGFR治疗的更糟糕的生存状况,但在接受免疫治疗的KRAS突变患者中改善了生存状况. CALGB/SWOG 80405数据证实了较短的PFS和OS,在治疗臂中具有较高的AXL.
结论:
- 在CRC中高AXL表达与免疫抑制的微环境和标准治疗的劣质结果有关.
- AXL确定了KRAS突变CRC患者的特定亚组,这些患者从免疫治疗中获得了显著的益处.
- 在CRC管理中,AXL作为特定环境的生物标志物和潜在的治疗标.
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