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化学基因表达预测T细胞炎症和检查点抑制改善的存活率在固体癌症中

Joan Miguel Romero^1,2, Emma Titmuss³, Yifan Wang^1,2,4

¹Research Institute of the McGill University Health Centre, Montréal, QC, Canada.

NPJ precision oncology

|August 9, 2023

概括

一种新的四种化基因签名 (c-Score) 通过识别瘤中的T细胞炎症标志来预测免疫检查点抑制剂 (ICI) 反应. 这种生物标志物在预测各种癌症类型的患者存活率方面优于瘤突变负担 (TMB).

科学领域:

免疫学和瘤学
癌症生物标志物癌症生物标志物
瘤微环境瘤微环境

背景情况:

免疫检查点抑制剂 (ICI) 在特定癌症中显示出有效性,因此需要更好的预测剂来进行更广泛的患者选择.
目前的生物标志物,如瘤突变负担 (TMB),在识别所有ICI响应性瘤方面存在局限性.
需要改善T细胞炎症标志物,以指导ICI治疗.

研究的目的:

为了研究四种化基因表达特征 (c-Score) 作为抗瘤免疫和ICI反应的预测指标.
评估c-Score与免疫检查点基因表达和癌症免疫周期特征的关联.
为了将c-Score与TMB的预测性表现与ICI治疗的患者存活结果进行比较.

主要方法:

对癌症基因组图谱 (TCGA) 数据的分析,以评估各种癌症类型的c-Score表达.
c-Score与免疫检查点基因和癌症免疫周期标记物的相关性.
泛癌队列的回顾性分析 (n=82) 和使用TIDE和PredictIO数据库对ICI治疗结果的验证.

主要成果:

高c-Score (c-Score^hi) 瘤表现出免疫检查点基因表达增加和癌症免疫周期的特征.
与c-Score^低患者相比,c-Score^hi患者在ICI治疗后的进展和整体存活时间明显较长.
在预测ICI治疗患者的整体存活率方面,c-Score的表现优于TMB.

结论:

c-Score有效地识别了T细胞炎症的瘤,表明了对ICI治疗的潜在反应.
这种化学基因签名作为一种更强大的预测生物标志物用于ICI治疗,而不是TMB跨多种癌症类型.
通过识别目前未被识别的响应子集,c-Score有可能扩大患者接受ICI治疗的资格.

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