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
CD3+ TIL（肿瘤浸润淋巴细胞）(TILs) 的异质性分布模式与高联合阳性评分 (CPS) 有利于切除后早期小细胞肺癌的预后
英文原题：Heterogeneous distribution pattern of CD3+ tumor-infiltrated lymphocytes (TILs) and high combined positive score (CPS) favored the prognosis of resected early stage small-cell lung cancer.
查看英文原题
Heterogeneous distribution pattern of CD3+ tumor-infiltrated lymphocytes (TILs) and high combined positive score (CPS) favored the prognosis of resected early stage small-cell lung cancer.
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研究概要
SCLC 的免疫微环境具有异质性。热点、CD3/CD4+ TIL 数量及 CPS 值在判断抗肿瘤免疫及预测 SCLC 患者临床结局方面具有价值。
研究思路结论见上方概要
目的
本研究旨在阐明小细胞肺癌（SCLC）免疫特征的异质性。
方法
对来自根治性切除术的55例SCLC FFPE样本进行了CD3、CD4、CD8和PD-L1的免疫组织化学（IHC）染色。对CD3+TIL（肿瘤浸润淋巴细胞）（TILs）进行定量评估，以呈现肿瘤和间质区域中的异质性。评估TILs的热点区域，以阐明TIL密度与其免疫能力之间的潜在关系。评估了在肿瘤TILs（t-TILs）和间质TILs（s-TILs）上表达的programmed death ligand-1（PD-L1），并以肿瘤阳性评分（TPS）和联合阳性评分（CPS）的数值进行定量描述。根据TPS和CPS与无病生存期（DFS）的关系，进一步确定了它们的临床价值。
结果
肿瘤间质中观察到的CD3+ TILs比实质内更丰富（15.02 2.25% vs. 1.58 0.35%）。CD3+ s-TILs的数量与DFS呈正相关。CD3+/CD4+ TILs亚群相比CD3+/CD8+亚群对DFS更有利。在肿瘤区域观察到CD3+ TILs热点，CD3+ TILs热点更多的患者预后更好。CPS比TPS更能可靠地描述SCLC中PD-L1的表达，并且发现其与肿瘤大小和DFS呈正相关。
展开英文摘要原文
PURPOSE
This study aimed to illustrate the heterogeneity of immune features in small cell lung cancer (SCLC).
METHODS
Immunohistochemistry (IHC) staining of CD3, CD4, CD8 and PD-L1 were performed with 55 SCLC FFPE samples from radical resections. Quantitative assessment of CD3+ tumor-infiltrated lymphocytes (TILs) to present the heterogeneity in the tumor and the stroma areas. Hotspots of TILs were evaluated to illustrate the potential relationship between TIL-density and its immune competence. Programmed death ligand-1 (PD-L1) expressed on both tumor TILs (t-TILs) and stroma TILs (s-TILs) was evaluated and quantitatively described as values of tumor positive score (TPS) and combined positive score (CPS). The clinical value of TPS and CPS were further identified according to their relationship with disease-free survival (DFS).
RESULTS
More abundant CD3+ TILs were observed in the tumor stroma than that within the parenchyma (15.02 2.25% vs. 1.58 0.35%) . The amount of CD3+ s-TILs were positively correlated with DFS. The CD3+/CD4+ subset of the TILs was found more favorable to DFS compared to the CD3+/CD8+ subset. Hotspots of CD3+ TILs were observed in tumor regions and patients with more Hotspots of CD3+ TILs have better outcomes. CPS were more reliable than TPS to describe PD-L1 expression in SCLC and it was found positively correlated with tumor size and DFS.
CONCLUSIONS
The immune microenvironment of SCLC was heterogeneous. Hotspots, the amount of CD3/CD4+ TILs and the CPS value were found valuable in determine the anti-tumor immunity and predicting the clinical outcome of SCLC patients.
论文信息
- 作者
- Zhu L、Cheng G、Wu M、Chen M、Jin Y
- 第一作者单位
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China.China
- 通讯作者单位
- Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China; Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang 310022, China. Electronic address: jinying@zjcc.org.cn.China
- 期刊
- Translational oncology2023 Aug
- 原文标识
- PubMed 37267802 · DOI 10.1016/j.tranon.2023.101697
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