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
非小细胞肺癌肿瘤微环境中浸润免疫细胞的空间异质性
英文原题：Spatial heterogeneity of infiltrating immune cells in the tumor microenvironment of non-small cell lung cancer.
查看英文原题
Spatial heterogeneity of infiltrating immune cells in the tumor microenvironment of non-small cell lung cancer.
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中文摘要
TIL（肿瘤浸润淋巴细胞）是非小细胞肺癌（NSCLC）肿瘤微环境（TME）的重要组成部分，但由于其异质性，难以进行描述。
本研究分析了 NSCLC 患者的 5 种细胞标志物。我们使用 EfficientNet-B3 对肿瘤细胞（TC）和 TIL 进行分割，并分析其数量信息及空间分布。随后，通过叠加连续切片的单显色免疫组织化学（IHC）图像，模拟多重免疫组化（mIHC）。
结果显示，程序性死亡配体 1（PD-L1）阳性肿瘤细胞的比例和密度在肿瘤核心区最高。CD8+ T 细胞距离肿瘤最近（中位距离 41.71 μm），而 PD-1+ T 细胞距离最远（中位距离 62.2 μm）；大多数淋巴细胞聚集在肿瘤周围 10–30 μm 的范围内，可能在此与肿瘤细胞发生相互作用。
我们还发现，可依据 CD8+ T 细胞密度对 TME 进行分类，该指标与患者预后相关。此外，我们以 CD4 染色 IHC 切片为基础，实现了单显色 IHC 切片的叠加显示。
本研究探究了 NSCLC 患者异质性 TME 中细胞的数量和空间分布，并实现 TME 分类；同时提出了一种以较低成本展示多种分子共表达的方法。
展开英文摘要原文
Tumor-infiltrating lymphocytes (TILs) are essential components of the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). Still, it is difficult to describe due to their heterogeneity. In this study, five cell markers from NSCLC patients were analyzed.
We segmented tumor cells (TCs) and TILs using Efficientnet-B3 and explored their quantitative information and spatial distribution. After that, we simulated multiplex immunohistochemistry (mIHC) by overlapping continuous single chromogenic IHCs slices. As a result, the proportion and the density of programmed cell death-ligand 1 (PD-L1)-positive TCs were the highest in the core.
CD8+ T cells were the closest to the tumor (median distance: 41. 71 m), while PD-1+T cells were the most distant (median distance: 62. 2 m), and our study found that most lymphocytes clustered together within the peritumoral range of 10-30 m where cross-talk with TCs could be achieved.
We also found that the classification of TME could be achieved using CD8+ T-cell density, which is correlated with the prognosis of patients.
In addition, we achieved single chromogenic IHC slices overlap based on CD4-stained IHC slices.
We explored the number and spatial distribution of cells in heterogeneous TME of NSCLC patients and achieved TME classification.
We also found a way to show the co-expression of multiple molecules economically.
论文信息
- 作者
- Liu X、Kong Y、Qian Y、Guo H、Zhao L、Wang H、Xu K、Ye L
- 第一作者单位
- Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; School of Medicine, Tongji University, Shanghai 200092, China.China
- 通讯作者单位
- Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China; School of Medicine, Tongji University, Shanghai 200092, China. Electronic address: 2250601@qq.com.China
- 期刊
- Translational oncology2024 Dec
- 原文标识
- PubMed 39366301 · DOI 10.1016/j.tranon.2024.102143
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