在癌症中具有临床和免疫学相关的TIM-3转录组景观
Jibran Ahmed1, Daisuke Nishizaki2, Hirotaka Miyashita3
1Developmental Therapeutics Clinic, Division of Cancer Treatment and Diagnosis, National Cancer Institute, National Institute of Health Bethesda, MD, The United Sates.
American journal of cancer research
|June 11, 2024
概括
瘤中的高TIM-3RNA表达与PD-L2和VISTA等其他免疫检查点相关,在胰腺癌中很常见. 在接受免疫检查点抑制剂 (ICI) 治疗的患者中,它预测了更长的生存期.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 基因组学就是基因组学.
背景情况:
- 含有-3 (TIM-3) 的T细胞免疫球蛋白和粘素域是一种抑制检查点受体,与抗PD-1/抗PD-L1 免疫检查点抑制剂 (ICI) 的耐药性有关.
- 用ICI治疗的高级固体瘤中TIM-3RNA表达的预测和预后价值在很大程度上仍未确定.
研究的目的:
- 在各种高级固体瘤中研究TIM-3的转录基因表达.
- 评估TIM-3表达与ICI治疗患者的临床结果之间的关联.
- 探索TIM-3表达与其他免疫检查点分子之间的关系.
主要方法:
- 从OmniSeq数据库分析了TIM-3RNA表达数据,涉及31种癌症类型的514名患者.
- 校准了TIM-3转录组模式,并将其表达为与参考人群相对的百分位数.
- 进行了统计分析,包括多变量分析,以评估与PD-L2,VISTA,总生存率 (OS) 和无进展生存率 (PFS) 的相关性.
主要成果:
- 90种瘤 (17.5%) 呈现高TIM-3RNA表达率 (≥75百分位数),胰腺癌呈现最高比例 (36%).
- 高TIM-3表达与高PD-L2 (OR 9.63,P<0.001) 和高VISTARNA表达 (OR 2.71,P=0.002) 显著相关.
- 在ICI治疗的患者中,高TIM-3表达预测了更长的中位数生存期 (2.84与1.21年,P=0.0033),但不是PFS,并且不是非ICI治疗的患者的预后因素.
结论:
- 在癌症类型之间和癌症类型内,TIM-3RNA表达有显著的变化,高水平与PD-L2,VISTA和胰腺癌相关.
- 高TIM-3表达可以作为预测生物标志物,改善ICI治疗患者的整体存活率.
- 对于精确免疫疗法策略,需要进一步研究单个瘤免疫学概况和共同表达检查点的共同向.
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