Single cell analysis of pan-cancer tumor microenvironment in immunotherapy.

IF 3.2 2区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Human molecular genetics Pub Date : 2025-08-21 DOI:10.1093/hmg/ddaf101

Feng Li, Ke Xue, Liying Pei, Yu Sun, Zhe Chen, Yifang Zhang, Kaiyue Song, Wensong Liu, Quan Qi, Xue Gong, Jing Li, Yanjun Xu

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Abstract

The high heterogeneity of tumor microenvironment (TME) is a key factor affecting immunotherapy. We integrated immunotherapy related scRNA-seq and bulk datasets to analyze the TME, mine key factors and dissect the mechanism in immunotherapy. Analyzing the cell composition of TME in cancer immunotherapy, we revealed key TME cell types, including B cells, CD8+ T cells and fibroblasts. Through cell subsets identification, pseudo-time sequence and functional status analysis of malignant cells, it was found that the functional status of malignant cell was heterogeneous under different immunotherapy conditions. Key cellular interactions in cancer immunotherapy were also revealed. Further, 16 marker genes and 6 marker cell types of cancer immunotherapy were identified, and then gene and cell model were constructed to predict the immunotherapy response of individuals, and the model were evaluated based on multiple independent validation datasets. This study can provide important guidance for improving the efficiency and understanding the mechanism of cancer immunotherapy.

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免疫治疗中泛癌肿瘤微环境的单细胞分析。

肿瘤微环境（TME）的高度异质性是影响免疫治疗的关键因素。我们整合了免疫治疗相关的scRNA-seq和大量数据集来分析TME，挖掘关键因素并剖析免疫治疗的机制。我们分析了肿瘤免疫治疗中TME的细胞组成，揭示了关键的TME细胞类型，包括B细胞、CD8+ T细胞和成纤维细胞。通过对恶性细胞亚群鉴定、伪时间序列和功能状态分析，发现不同免疫治疗条件下恶性细胞的功能状态存在异质性。癌症免疫治疗中的关键细胞相互作用也被揭示。进一步，鉴定出肿瘤免疫治疗的16个标记基因和6种标记细胞类型，构建预测个体免疫治疗反应的基因和细胞模型，并基于多个独立验证数据集对模型进行评估。本研究可为提高肿瘤免疫治疗的效率和理解肿瘤免疫治疗的机制提供重要的指导。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human molecular genetics 生物-生化与分子生物学

CiteScore

6.90

自引率

2.90%

发文量

294

审稿时长

2-4 weeks

期刊介绍： Human Molecular Genetics concentrates on full-length research papers covering a wide range of topics in all aspects of human molecular genetics. These include: the molecular basis of human genetic disease developmental genetics cancer genetics neurogenetics chromosome and genome structure and function therapy of genetic disease stem cells in human genetic disease and therapy, including the application of iPS cells genome-wide association studies mouse and other models of human diseases functional genomics computational genomics In addition, the journal also publishes research on other model systems for the analysis of genes, especially when there is an obvious relevance to human genetics.