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:Tissue-matched analysis of MRI evaluating the tumor infiltrating lymphocytes in hepatocellular carcinoma.
Tissue-matched analysis of MRI evaluating the tumor infiltrating lymphocytes in hepatocellular carcinoma.
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TIL(肿瘤浸润淋巴细胞)在肿瘤微环境和免疫治疗应答中发挥关键作用。本研究旨在探索多参数磁共振成像(MRI)评估TIL的可行性,并建立考虑空间异质性的评估模型。研究对肝细胞癌(HCC)小鼠(N=28)进行多参数MRI。采用3D打印辅助组织取样,将多参数MRI数据与肿瘤组织相匹配,随后进行流式细胞术和新一代RNA测序。使用Pearson相关、多变量逻辑回归和受试者工作特征(ROC)曲线分析构建TIL相关MRI参数模型。包括T1弛豫时间和灌注在内的MRI定量参数与肿瘤组织中白细胞、T细胞、CD4+ T细胞、CD8+ T细胞、PD-1+CD8+ T细胞、B细胞、巨噬细胞和调节性T细胞浸润相关,相关系数范围为-0.656至0.482(p<0.05)。TIL被分为炎症型和非炎症型亚组;炎症组中T细胞、CD8+ T细胞和PD-1+CD8+ T细胞比例均显著高于非炎症组,分别为43.37%对25.45%、50.83%对34.90%、40.45%对29.47%(均p<0.001)。基于Kep和T1post组合Z评分构建的TIL评估模型能够区分两组,曲线下面积为0.816(95% CI:0.721–0.910),截值为-0.03(敏感度68.4%,特异度91.3%)。
此外,Z评分与T细胞活化、趋化因子生成及细胞黏附相关基因表达有关。将组织匹配分析与多参数MRI结合,为区域性评估提供了可行方法,并能够区分不同TIL亚型。
Tumor-infiltrating lymphocytes (TILs) play critical roles in the tumor microenvironment and immunotherapy response.
This study aims to explore the feasibility of multi-parametric magnetic resonance imaging (MRI) in evaluating TILs and to develop an evaluation model that considers spatial heterogeneity. Multi-parametric MRI was performed on hepatocellular carcinoma (HCC) mice (N = 28). Three-dimensional (3D) printing was employed for tissue sampling, to match the multi-parametric MRI data with tumor tissues, followed by flow cytometry analysis and next-generation RNA-sequencing. Pearson's correlation, multivariate logistic regression, and receiver operating characteristic (ROC) curve analyses were utilized to model TIL-related MRI parameters.
MRI quantitative parameters, including T1 relaxation times and perfusion, were correlated with the infiltration of leukocytes, T-cells, CD4+ T-cells, CD8+ T-cells, PD1 + CD8+ T-cells, B-cells, macrophages, and regulatory T-cells (correlation coefficients ranged from -0. 656 to 0. 482, p <. 05) in tumor tissues. TILs were clustered into inflamed and non-inflamed subclasses, with the proportion of T-cells, CD8+ T-cells, and PD1 + CD8+ T-cells significantly higher in the inflamed group compared to the non-inflamed group (43.
37% vs. 25. 45%, 50. 83% vs. 34. 90%, 40. 45% vs. 29. 47%, respectively; p <. 001). The TIL evaluation model, based on the Z-score combining Kep and T1post, was able to distinguish between these subgroups, yielding an area under the curve of 0. 816 (95% confidence interval 0. 721-0. 910) and a cut-off value of -0. 03 (sensitivity 68. 4%, specificity 91. 3%).
Additionally, the Z-score was related to the gene expression of T-cell activation, chemokine production, and cell adhesion. The tissue-matched analysis of multi-parametric MRI offers a feasible method of regional evaluation and can distinguish between TIL subclasses.
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