为肝细胞癌武装 GPC3 CAR-T 细胞:多少才足够,下一步是什么?
Armouring GPC3 CAR T cells for hepatocellular carcinoma: how much is enough and what comes next?
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:AI-based tumor-infiltrating lymphocyte scoring system for assessing HCC prognosis in patients undergoing liver resection.
AI-based tumor-infiltrating lymphocyte scoring system for assessing HCC prognosis in patients undergoing liver resection.
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我们开发了一种自动化系统,利用 CD8 染色的全切片图像来评估免疫浸润(ATLS-8)。
TIL(肿瘤浸润淋巴细胞)(TILs),尤其是CD8+ TILs,是许多癌症中的关键预后标志物。然而,其在肝细胞癌(HCC)中的预后价值仍存在争议,证据不一。鉴于接受肝切除术的HCC患者结局具有异质性,本研究旨在开发一种基于AI的系统来量化CD8+ TILs,并评估其对HCC患者的预后价值。
我们开展了一项回顾性多中心研究,纳入三个队列中接受肝切除术的患者(N = 514)。我们训练了一个深度神经网络和一个随机森林模型,用于在H&E和CD8染色全切片图像中分割肿瘤区域并定位CD8+ TIL。我们量化了CD8+ TIL密度,并建立了自动化CD8+TIL(肿瘤浸润淋巴细胞)评分(ATLS-8)系统,以评估其预后价值。
在发现队列中,ATLS-8低评分组和ATLS-8高评分组的5年OS率分别为34.05%和65.03%(HR 2.40;95% CI,1.37-4.19;p = 0.015)。这些发现在验证队列1中得到证实,其5年OS率分别为28.57%和68.73%(HR 3.38;95% CI,1.27-9.02;p = 0.0098),在验证队列2中分别为59.26%和81.48%(HR 2.74;95% CI,1.05-7.15;p = 0.031)。ATLS-8改善了基于临床变量的预后模型(三个队列中C-index分别为0.770 vs. 0.757;0.769 vs. 0.727;0.712 vs. 0.642)。
We conducted a retrospective multicenter study on patients undergoing liver resection across three cohorts (N = 514). We trained a deep neural network and a random forest model to segment tumor regions and locate CD8+ TILs in H&E and CD8-stained whole-slide images. We quantified CD8+ TIL density and established an Automated CD8+ Tumor-infiltrating Lymphocyte Scoring (ATLS-8) system to assess its prognostic value.
In the discovery cohort, the 5-year overall survival (OS) rates were 34.05% for ATLS-8 low-score and 65.03% for ATLS-8 high-score groups (hazard ratio [HR] 2.40; 95% CI, 1.37-4.19; p = 0.015). These findings were confirmed in validation cohort 1, which had 5-year OS rates of 28.57% and 68.73% (HR 3.38; 95% CI, 1.27-9.02; p = 0.0098), and validation cohort 2, which had 59.26% and 81.48% (HR 2.74; 95% CI, 1.05-7.15; p = 0.031). ATLS-8 improved the prognostic model based on clinical variables (C-index 0.770 vs. 0.757; 0.769 vs. 0.727; 0.712 vs. 0.642 in three cohorts).
We developed an automated system using CD8-stained whole-slide images to assess immune infiltration (ATLS-8). In patients with HCC undergoing resection, higher CD8+ TIL density correlates with better OS, as per ATLS-8 assessment. This system is a promising tool for advancing clinical immune microenvironment assessment and outcome prediction. IMPACT AND IMPLICATIONS: CD8+ tumor-infiltrating lymphocytes (TILs) have been identified as a prognostic factor associated with many cancers. In this study, CD8+ TILs were identified as an independent prognostic factor for overall survival in patients with hepatocellular carcinoma who undergoing liver resection. Therefore, ATLS-8, a novel digital biomarker based on whole-slide image-level CD8+ TILs, could play an important role in the prognostic assessment of patients with HCC and could be integrated into clinicopathological models to participate in the decision-making and prognostic assessment of patients. The scoring system combined with artificial intelligence is essential for automated, quantitative, whole-slide image-level assessment of TILs, which can be widely applied to quantify the immune profile of multi-cancer disease types with the discussion of subsequent immunotherapy.
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