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人工智能驱动的 TIL(肿瘤浸润淋巴细胞)空间分析作为非小细胞肺癌免疫检查点抑制的补充生物标志物

英文原题:Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as Complementary Biomarker for Immune Checkpoint Inhibition in Non-Small-Cell Lung Cancer.

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Artificial Intelligence-Powered Spatial Analysis of Tumor-Infiltrating Lymphocytes as Complementary Biomarker for Immune Checkpoint Inhibition in Non-Small-Cell Lung Cancer.

PubMed 2022/03/10(内容时间) J Clin Oncol Q1 · IF 44.7(JCR 2025)

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研究概要

AI 驱动的 TIL 空间分析与晚期 NSCLC 中 ICI 的肿瘤缓解和无进展生存期相关。这可能是病理学家确定的 TPS 的潜在补充生物标志物。

研究思路结论见上方概要

基于TIL(肿瘤浸润淋巴细胞)的生物标志物在预测免疫检查点抑制剂(ICI)疗效方面具有潜在价值。然而,由于方法学局限性以及全切片图像(WSI)中TIL分布空间分析过程繁琐,临床应用仍面临挑战。

我们开发了一种人工智能(AI)驱动的WSI分析仪,用于分析肿瘤微环境中的TIL,能够定义三种免疫表型(IP):炎症型、免疫排斥型和免疫荒漠型。这些IP与两个独立晚期非小细胞肺癌(NSCLC)患者队列中的肿瘤对ICI的应答及生存相关。

与免疫排斥型或免疫荒漠型表型患者相比,炎症型IP与局部免疫细胞溶解活性富集、更高的缓解率和更长的无进展生存期相关。在WSI水平上,AI模型确定的肿瘤比例评分(TPS)与病理学家分析的对照TPS之间存在显著正相关(P < .001)。总体而言,44.0%的肿瘤为炎症型,37.1%为免疫排斥型,18.9%为免疫荒漠型。在programmed death ligand-1 TPS < 1%、1%-49%和50%的患者中,炎症型IP的发生率分别为31.7%、42.5%和56.8%。炎症型IP的中位无进展生存期和总生存期分别为4.1个月和24.8个月,免疫排斥型IP为2.2个月和14.0个月,免疫荒漠型IP为2.4个月和10.6个月。

展开英文摘要原文

Biomarkers on the basis of tumor-infiltrating lymphocytes (TIL) are potentially valuable in predicting the effectiveness of immune checkpoint inhibitors (ICI). However, clinical application remains challenging because of methodologic limitations and laborious process involved in spatial analysis of TIL distribution in whole-slide images (WSI).

We have developed an artificial intelligence (AI)-powered WSI analyzer of TIL in the tumor microenvironment that can define three immune phenotypes (IPs): inflamed, immune-excluded, and immune-desert. These IPs were correlated with tumor response to ICI and survival in two independent cohorts of patients with advanced non-small-cell lung cancer (NSCLC).

Inflamed IP correlated with enrichment in local immune cytolytic activity, higher response rate, and prolonged progression-free survival compared with patients with immune-excluded or immune-desert phenotypes. At the WSI level, there was significant positive correlation between tumor proportion score (TPS) as determined by the AI model and control TPS analyzed by pathologists ( P < .001). Overall, 44.0% of tumors were inflamed, 37.1% were immune-excluded, and 18.9% were immune-desert. Incidence of inflamed IP in patients with programmed death ligand-1 TPS at < 1%, 1%-49%, and 50% was 31.7%, 42.5%, and 56.8%, respectively. Median progression-free survival and overall survival were, respectively, 4.1 months and 24.8 months with inflamed IP, 2.2 months and 14.0 months with immune-excluded IP, and 2.4 months and 10.6 months with immune-desert IP.

The AI-powered spatial analysis of TIL correlated with tumor response and progression-free survival of ICI in advanced NSCLC. This is potentially a supplementary biomarker to TPS as determined by a pathologist.

论文信息

作者
Park S、Ock CY、Kim H、Pereira S、Park S、Ma M、Choi S、Kim S
单位
Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Republic of Korea.South Korea
文献类型
非美国政府资助研究
期刊
Journal of clinical oncology : official journal of the American Society of Clinical Oncology2022 Jun 10
原文标识
PubMed 35271299 · DOI 10.1200/JCO.21.02010