在细胞癌中,免疫检查点抑制的异常反应的免疫基因组决定因素
Tejas Jammihal1,2, Renee Maria Saliby3,4, Chris Labaki3,5
1Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Nature cancer
|January 9, 2025
概括
转移性清细胞细胞癌 (mccRCC) 免疫治疗的异常反应与使用PD1/PDL1和CTLA4抑制剂的高新抗原负载有关. 相比之下,PD1/PDL1和VEGF抑制剂显示B细胞活性和三级淋巴体结构与异常反应相关.
科学领域:
- 在瘤学瘤学.
- 免疫学 免疫学 免疫学
- 基因组学就是基因组学.
背景情况:
- 在转移性清细胞细胞癌 (mccRCC) 中,对免疫检查点抑制剂 (ICI) 的异常反应是持久的,但不太了解.
- 在mccRCC中,免疫疗法异常反应 (ER) 的分子驱动因素尚未完全阐明.
研究的目的:
- 在接受标准护理免疫疗法的未接受治疗的mccRCC患者中研究ER的分子基础.
- 在不同的免疫疗法方案中识别与ER相关的独特生物特征.
主要方法:
- 从mccRCC患者的治疗前基因组和转录组数据的分析.
- 在两个不同的免疫治疗队伍中,ER和非ER患者之间的分子概况的比较:PD1/PDL1 + CTLA4抑制剂 (IO/IO) 和PD1/PDL1 + VEGF抑制剂 (IO/VEGF).
主要成果:
- 在IO/IO队列中,ER与显著更高的克隆新抗原负载有关.
- 在IO/VEGF队列中,ER参与者表现出B细胞受体信号通路的丰富,三级淋巴体结构 (TLS) 签名,以及代谢活动的增加.
结论:
- 在mccRCC中,异常反应可能由不同的机制驱动,这取决于所使用的免疫疗法组合.
- 克隆新抗原驱动的T细胞反应和TLS形成似乎对IO/IO环境中的ER至关重要.
- 在IO/VEGF环境中,B细胞导向免疫和瘤代谢活性增加可能导致ER.
- 未来的治疗策略应考虑结合T细胞和B细胞抗瘤免疫力,以提高ccRCC的疗效.
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