一种用于克服非小细胞肺癌治疗中抗原异质性的多靶向 CAR-T 细胞平台
A Multi-Targeting Chimeric Antigen Receptor-T Cell Platform to Overcome Antigen Heterogeneity in the Treatment of Non-Small Cell Lung Cancer.
这些发现支持采用多靶点CAR-T 策略来应对NSCLC及可能其他实体瘤中的抗原异质性。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
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.
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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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。
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。
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.
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