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:Tumor-Infiltrating Lymphocyte Aggregation Refines Prognosis in Patients With Hepatocellular Carcinoma.
Tumor-Infiltrating Lymphocyte Aggregation Refines Prognosis in Patients With Hepatocellular Carcinoma.
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TIL(肿瘤浸润淋巴细胞)(TILs)在肝细胞癌(HCC)中的预后作用仍不明确。本研究探讨了早期HCC组织中TIL聚集与患者生存之间的关联。回顾性分析了353例接受根治性肝切除术的HCC患者的个体患者水平数据。使用人工神经网络算法分析TIL聚集,以在苏木精-伊红染色的全切片图像中定义免疫表型(IPs)。比较了各IP之间TIL聚集与生存的关联,并结合临床变量验证了一种优化的TIL表型。在使用人工神经网络算法测量的8个IP特征中,TIL密度K50——一种根据每个细胞与最近50个淋巴细胞的距离为其分配密度而生成的指标——在单因素分析(风险比,0.282;95% CI,0.181-0.439;P < .0001)和校正临床因素后的多因素分析(风险比,0.315;95% CI,0.115-0.860;P = .024)中均与无病生存期改善相关。当TIL密度K50与临床因素结合时(TIL-临床整合[TCI]模型),在训练队列中,无病生存期和总生存期的曲线下面积性能分别提高至0.798和0.781,在验证队列中分别为0.759和0.723。
此外,亚组分析表明,其预测价值对极晚期复发和长达<8年的生存尤为显著。HCC组织中丰富的TILs与晚期复发风险降低和生存改善相关,提示TILs在早期HCC中可能具有时间依赖性的预后作用。
The prognostic role of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) remains elusive.
This study explored the association between TIL aggregation in early-stage HCC tissues and patient survival. Individual patient-level data from 353 patients diagnosed with HCC who underwent radical hepatectomy were retrospectively analyzed. TIL aggregation was analyzed using an artificial neural network algorithm to define the immune phenotypes (IPs) within hematoxylin and eosin-stained whole-slide images. The association between TIL aggregation and survival was compared among IPs, and an optimized TIL phenotype was validated with clinical variables.
Among the 8 IP features measured using the artificial neural network algorithm, TIL density K50 , a metric generated by an assigned density of each cell based on its distance with the 50 nearest lymphocytes, was associated with improved disease-free survival in univariate (hazard ratio, 0. 282; 95% CI, 0. 181-0. 439; P < . 0001) and multivariate analyses (hazard ratio, 0.
315; 95% CI, 0. 115-0. 860; P = . 024) after adjusting for clinical factors. When TIL density K50 is combined with clinical factors (TIL-clinical-integrated [TCI] model), area under the curve performance for disease-free survival and overall survival was improved to 0. 798 and 0. 781 in the training cohort and 0. 759 and 0. 723 in the validation cohort, respectively.
Furthermore, subgroup analyses indicated that its predictive value is particularly strong for very late recurrence and survival up to <8 years. Abundant TILs in HCC tissue are associated with reduced late recurrence risk and improved survival, suggesting a potential time-dependent prognostic role of TILs in early-stage HCC.
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