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
CD1B 是一种潜在的预后生物标志物，与肿瘤突变负荷相关，并在肺腺癌中促进抗肿瘤免疫
英文原题：CD1B is a Potential Prognostic Biomarker Associated with Tumor Mutation Burden and Promotes Antitumor Immunity in Lung Adenocarcinoma.
查看英文原题
CD1B is a Potential Prognostic Biomarker Associated with Tumor Mutation Burden and Promotes Antitumor Immunity in Lung Adenocarcinoma.
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研究概要
我们的研究构建了一个 TMB 预后模型，有效预测了 LUAD 患者的预后。CD1B 表达与更好的预后相关，并在 LUAD 中促进抗肿瘤免疫，这可能作为 LUAD 潜在的预后生物标志物和免疫相关治疗靶点。
研究思路结论见上方概要
目的
肿瘤突变负荷（TMB）和TIL（肿瘤浸润淋巴细胞）（TILs）已被公认为免疫治疗反应性的分子决定因素。本研究旨在构建TMB预后模型，并探索对肺腺癌（LUAD）预后和治疗效果具有预测潜力的生物标志物。
方法
利用TCGA、GEO和Immport数据库分析LUAD的突变谱和免疫浸润。计算TMB评分并进行差异分析以识别TMB相关基因。随后，应用Cox回归模型和生存分析识别预后基因并构建TMB预后模型。通过免疫组化（IHC）在92例患者组织样本中进一步验证CD1B的表达和预后价值。进行GSEA分析CD1B表达相关的信号通路。
结果
高TMB样本表现出更高的CD8+ T细胞、CD4+记忆T细胞和M1巨噬细胞浸润。共鉴定出397个TMB相关差异表达基因，其中47个为免疫相关基因。Cox回归分析确定了3个具有预后效应的核心TMB相关免疫基因（CD1B、SCGB3A1和VEGFD），并构建了TMB预后模型。该模型在训练集（TCGA）和测试集（GEO）中均表现出稳健的预测能力。值得注意的是，CD1B被确定为独立预后因素。临床样本IHC显示，CD1B低表达与较差的总生存期和晚期病理分期相关。此外，CD1B与大多数免疫检查点分子（包括PD-L1）之间存在强正相关。CD1B表达与LUAD中的免疫细胞浸润和免疫激活相关。
展开英文摘要原文
PURPOSE
Tumor mutation burden (TMB) and tumor-infiltrating lymphocytes (TILs) have been well recognized as molecular determinants of immunotherapy responsiveness. In this study, we aimed to construct a TMB prognostic model and explore biomarkers that have predictive potential for prognosis and therapeutic effect in lung adenocarcinoma (LUAD).
PATIENTS AND METHODS
The TCGA, GEO and Immport databases were used to analyze the mutation profiles and immune infiltration of LUAD. TMB scores were calculated and differential analysis was conducted to identify TMB-related genes. Then, Cox regression model and survival analysis were applied to identify the prognostic genes and construct a TMB prognostic model. The expression and prognostic value of CD1B were further verified by immunohistochemistry (IHC) in 92 patient tissue samples. GSEA was performed to analyze the signaling pathways associated with CD1B expression.
RESULTS
High-TMB samples exhibited higher infiltration of CD8+ T cells, CD4+ memory T cells, and M1 macrophages. A total of 397 TMB-related differentially expressed genes were identified, of which 47 were immune-related genes. Cox regression analyses determined 3 hub TMB-related immune genes (CD1B, SCGB3A1, and VEGFD) with prognostic effects, and a TMB prognostic model was constructed. The model demonstrated robust predictive ability in both the training (TCGA) and testing (GEO) datasets. Notably, CD1B was identified as an independent prognostic factor. IHC of clinical samples showed that low expression of CD1B was related to poor overall survival and advanced pathological stages. In addition, there was a strong positive correlation between CD1B and most immune checkpoint molecules, including PD-L1. CD1B expression was associated with immune cell infiltration and immune activation in LUAD.
CONCLUSION
Our study constructed a TMB prognostic model that effectively predicted the prognosis of LUAD patients. CD1B expression is correlated with better prognosis and promotes antitumor immunity in LUAD, which may serve as a potential prognostic biomarker and immune-related therapeutic target for LUAD.
论文信息
- 作者
- Li Z、Feng Y、Li P、Wang S、Liu X、Xia S
- 单位
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.China
- 期刊
- International journal of general medicine2022
- 原文标识
- PubMed 35418778 · DOI 10.2147/IJGM.S352851
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