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弥漫大 B 细胞淋巴瘤 CAR-T 制备中 CD3(+) 细胞采集产量的预测性生物标志物验证:机器学习方法

英文原题:Predictive biomarkers validation of CD3(+) cell apheresis yield in CAR-T manufacturing for diffuse large B-cell lymphoma: a machine learning approach.

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Predictive biomarkers validation of CD3(+) cell apheresis yield in CAR-T manufacturing for diffuse large B-cell lymphoma: a machine learning approach.

PubMed 2025/11/28(内容时间) Sci Rep Q1 · IF 4.9(JCR 2025)

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中文摘要

嵌合抗原受体(CAR)T细胞疗法在治疗弥漫性大B细胞淋巴瘤(DLBCL)方面已取得显著成功。其初始步骤涉及通过单采术采集自体CD3 + 淋巴细胞,其中获得足够的CD3 + 细胞产量对于治疗效果至关重要。尽管已有先前研究,影响CD3 + 细胞单采术的因素仍知之甚少。传统统计分析提供的见解有限,但机器学习(ML)方法凭借其先进的模式识别能力,能够对临床预测因子进行精确建模。

在本研究中,我们采用了三种ML算法——随机森林分类器(RF)、逻辑回归(LR)和极端梯度提升(XGBoost),来分析一个由98名接受单核细胞(MNC)单采术的DLBCL患者组成的同质性队列。LR模型达到了0.824的曲线下面积(AUC),并识别出四个关键预测特征:CD3 + 细胞绝对计数、NK细胞百分比、总血容量和CD3 + 细胞百分比。其中,NK细胞百分比和CD3 + 细胞绝对计数对CD3 + 细胞单采术产量显示出最显著的负面影响。

本研究强调了ML方法作为一种补充分析方法的潜力,可用于识别影响CD3 + 细胞单采术效率的关键因素,为优化DLBCL患者的CAR-T 治疗结果提供了有价值的见解。

展开英文摘要原文

Chimeric antigen receptor (CAR) T-cell therapy has shown significant success in treating diffuse large B-cell lymphoma (DLBCL). The initial step involves collecting autologous CD3 + lymphocytes through apheresis, in which obtaining an adequate CD3 + cell yield is essential for therapeutic efficacy. Despite prior research, the factors influencing CD3 + cell apheresis remain poorly understood. Traditional statistical analyses offer limited insights, but machine learning (ML) approaches enable precision modeling of clinical predictors owing to their advanced pattern-recognition capabilities.

In this study, we employed three ML algorithms, random forest classifier (RF), logistic regression (LR), and extreme gradient boosting (XGBoost) to analyze a homogeneous cohort of 98 DLBCL patients who underwent mononuclear cell (MNC) apheresis. The LR model, which achieved an area under the curve (AUC) of 0.

824, identified four key predictive features: CD3 + cell absolute count, NK cell percentage, total blood volume, and CD3 + cell percentage. Among these, NK cell percentage and CD3 + cell absolute count showed the most significant negative impact on CD3 + cell apheresis yield.

This study underscores the potential of ML approaches as a complementary analytical approach for identifying key factors that impact CD3 + cell apheresis efficiency, offering valuable insights for optimizing CAR-T therapy outcomes in patients with DLBCL.

论文信息

作者
Carbonell D、Rodríguez-Sosa A、Gómez-Serrano L、Pérez-Corral A、Ruano G、Galayo M、Panadero N、Rufián L
第一作者单位
Department of Hematology, Gregorio Marañón General University Hospital, Madrid, Spain. diegocarbonell3@gmail.com.Spain
通讯作者单位
Epigenetics of Gastrointestinal diseases research group, School of Pharmacy and Biomolecular Sciences, Royal College of Surgeons in Ireland, Dublin, Ireland. aroso491@gmail.com.Ireland
期刊
Scientific reports2025 Nov 28
原文标识
PubMed 41315532 · DOI 10.1038/s41598-025-27061-2