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炎症型免疫表型预测多种癌症类型中免疫检查点抑制剂治疗的有利临床结局

英文原题:Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types.

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Inflamed immune phenotype predicts favorable clinical outcomes of immune checkpoint inhibitor therapy across multiple cancer types.

PubMed 2024/02/14(内容时间) J Immunother Cancer Q1 · IF 11.7(JCR 2025)

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研究概要

基于 AI 的 IIP 可能代表一种实用、经济、具有临床可操作性且不受肿瘤类型限制的生物标志物,可预测多种肿瘤类型对 ICI 治疗的反应。

研究思路结论见上方概要

炎性免疫表型(IIP),定义为肿瘤内区域TIL(肿瘤浸润淋巴细胞)的富集,是一种有前景的、与肿瘤类型无关的免疫检查点抑制剂(ICI)治疗反应的生物标志物。然而,在人工组织病理学检查中,以客观且可重复的方式定义IIP具有挑战性。在此,我们研究基于人工智能(AI)的免疫表型,能够在多种实体瘤类型中预测ICI临床结局。

Lunit SCOPE IO 是一种深度学习模型,可基于 TIL 分析确定肿瘤微环境的免疫表型。我们在一个从多个机构回顾性收集的、涵盖超过 27 种实体瘤类型的 1,806 例接受 ICI 治疗的患者队列中,评估了 IIP 与 ICI 治疗结局在客观缓解率(ORR)、无进展生存期(PFS)和总生存期(OS)方面的相关性。

我们观察到总体 IIP 患病率为 35.2%,与非 IIP 患者相比,IIP 患者在接受 ICI 治疗后的 ORR(26.3% vs 15.8%)、PFS(中位 5.3 vs 3.1 个月,HR 0.68,95% CI 0.61 至 0.76)和 OS(中位 25.3 vs 13.6 个月,HR 0.66,95% CI 0.57 至 0.75)均显著更优(所有比较 p<0.001)。在亚组分析中,除微卫星不稳定/错配修复缺陷亚组外,IIP 在大多数主要患者亚组中总体上预示 favorable PFS。

展开英文摘要原文

The inflamed immune phenotype (IIP), defined by enrichment of tumor-infiltrating lymphocytes (TILs) within intratumoral areas, is a promising tumor-agnostic biomarker of response to immune checkpoint inhibitor (ICI) therapy. However, it is challenging to define the IIP in an objective and reproducible manner during manual histopathologic examination. Here, we investigate artificial intelligence (AI)-based immune phenotypes capable of predicting ICI clinical outcomes in multiple solid tumor types.

Lunit SCOPE IO is a deep learning model which determines the immune phenotype of the tumor microenvironment based on TIL analysis. We evaluated the correlation between the IIP and ICI treatment outcomes in terms of objective response rates (ORR), progression-free survival (PFS), and overall survival (OS) in a cohort of 1,806 ICI-treated patients representing over 27 solid tumor types retrospectively collected from multiple institutions.

We observed an overall IIP prevalence of 35.2% and significantly more favorable ORRs (26.3% vs 15.8%), PFS (median 5.3 vs 3.1 months, HR 0.68, 95% CI 0.61 to 0.76), and OS (median 25.3 vs 13.6 months, HR 0.66, 95% CI 0.57 to 0.75) after ICI therapy in IIP compared with non-IIP patients, respectively (p<0.001 for all comparisons). On subgroup analysis, the IIP was generally prognostic of favorable PFS across major patient subgroups, with the exception of the microsatellite unstable/mismatch repair deficient subgroup.

The AI-based IIP may represent a practical, affordable, clinically actionable, and tumor-agnostic biomarker prognostic of ICI therapy response across diverse tumor types.

论文信息

作者
Shen J、Choi YL、Lee T、Kim H、Chae YK、Dulken BW、Bogdan S、Huang M
第一作者单位
Department of Pathology, Stanford University School of Medicine, Stanford, California, USA jeannes@stanford.edu ock.chanyoung@lunit.io.United States
通讯作者单位
Lunit, Seoul, Korea (the Republic of) jeannes@stanford.edu ock.chanyoung@lunit.io.South Korea
文献类型
美国 NIH 资助研究 · 非美国政府资助研究
期刊
Journal for immunotherapy of cancer2024 Feb 14
原文标识
PubMed 38355279 · DOI 10.1136/jitc-2023-008339